Yoon, Wan Ki;Heo, Mi Jung;Lee, Ok Sang;Lim, Sung Cil
Korean Journal of Clinical Pharmacy
/
v.22
no.4
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pp.356-366
/
2012
Background: Chemotherapy-induced peripheral neuropathy (CIPN) involving sensory and motor nerve damage or dysfunction is a common and serious clinical problem that affects many patients receiving cancer treatment. This condition may pose challenges for the clinician to diagnose and manage, particularly in patients with coexisting conditions or disorders that involve the peripheral nervous system. Many chemotherapeutic agents used today are associated with the development of serious and dose-limiting CIPN that can adversely affect the administration of planned therapy and can impair quality of life by interference with the patients' activities of daily living. The most important clinical objective in the evaluation of patients with CIPN is to determine their level of functional impairment involving activities of daily living. These findings are used to make medical decisions to continue, modify, delay, or stop treatment. The most commonly reported drugs to cause CIPN include taxanes, platinum agents, vinca alkaloids, thalidomide, and bortezomib. We aimed to determine PN incidence during cisplatin, carboplatin and oxaliplatin administration. Methods: We collected data from 125 patients who received at least one cycle of cisplatin, carboplatin or oxaliplatin. They completed a self-reported questionnaire and items related to their disease and peripheral neuropathy. The investigators filled in part of items about disease and treatment. Patient Neurotoxicity Qeustionnaire developed by Bionumerik company were applied for PN assessment. Results: The incidences of sensory neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 23%, 56% and 50%. The incidences of motor neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 18%, 42% and 19%. The incidences of severe neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 13%, 28% and 14%. The incidences of PN were associated with cumulative dose but not age, gender and concurrent illness. 19.2% of the patients (24/125) were prescribed with gabapentin, nortriptyline or gabapentin plus nortriptyline to reduce these peripheral symptoms and 75% of the patients answered the drug were effective. Conclusion: Incidence of PN after cisplatin or oxaliplatin administration is cumulative dose-related. Physician-based assessments under-reported the incidence and severity of CIPN. To overcome this limitation, diagnostic tools specifically designed to assess peripheral neuropathy severity associated with chemotherapy must be developed.
Journal of the Korean Society for Aeronautical & Space Sciences
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v.45
no.9
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pp.784-793
/
2017
A two-axis gimbal-type X-band antenna mounted on an observation satellite can efficiently transmit high-capacity image data to a ground station regardless of both the satellite position and the orbital motion. However, this X-band antenna induces unnecessary micro-jitter which can degrade the image quality of the high-resolution observation satellite. Therefore, to achieve the high-resolution image quality from the observation satellite, micro-jitters have been required to be isolated. In this study, to resolve aforementioned drawback, we proposed blade gear using a shape memory alloy (SMA) applied to azimuth stage of X-band antenna. To investigate the rotational basic characteristics of the proposed SMA blade gear, we performed rotational static loading test. Futhermore, to evaluate the cycle to failure of the gear, accelerated life test was conducted. The temperature test was conducted to confirm rotational basic characteristics at various temperature conditions. To verify the isolation performance for micro-jitter, we performed micro-jitter measurement test.
Kim Jun-Sung;Park Jin Hong;Park Sung-Jin;Kim Hyun Woo;Hua Jin;Cho Hyun Sun;Hwang Soon Kyung;Chang Seung Hee;Tehrani Arash Minai;Cho Myung Haing
Toxicological Research
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v.21
no.4
/
pp.347-353
/
2005
Eukaryotic initiation factor 4E (elF4E) is a key element for cap-dependent protein translation controlled by affinity between elF4E and 4E-binding protein 1 (4E-BP1). Rapamycin can also affect protein translation by regulating 4E-BP1 phosphorylation. Tobacco-specific nitrosamine, 4(N-methyl-N-nitrosamino )-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen, but its precise lung cancer induction mechanism remains unknown. Relative roles of cap-dependent and -independent protein translation in terms of NNK-induced lung carcinogenesis were elucidated using normal human bronchial epithelial cells. NNK concentrations applied in this study did not decrease cell viability. Addition of NNK restored rapamycin-induced decrease of protein synthesis and rapamycin-induced phosphorylation of 4E-BP1, and increased expression levels of mTOR, ERK1/2, p70S6K, and Raf-1 in a concentration-dependent manner. NNK also caused perturbation of normal cell cycle progression. Taken together, NNK might cause toxicity through the combination of restoration of 4E-BP1 phosphorylation and increase of elF4E as well as mTOR protein expression, interruption of Raf1/ERK as well as the cyclin G-associated p53 network. Our data could be applied towards elucidation of the molecular basis for lung cancer treatment.
Acetaminophen (APAP) overdose is known to cause severe hepatotoxicity mainly through the depletion of glutathione. In this study, we compared the cytotoxic effects of APAP on both a normal murine hepatic cell line, BNL CL.2, and its SV40-transformed cell line, BNL SV A.8. Gene expression profiles for APAP-treated cells were also obtained using microarray and analyzed to identify differences in genes or profiles that may explain the differences of susceptibility to APAP in these cell lines. These two cell lines exhibited different susceptibilities to APAP (0-$5,000{\mu}M$); BNL SV A.8 cells were more susceptible to APAP treatment compared to BNL CL.2 cells. A dose of $625{\mu}M$ APAP, which produced significant differences in cytotoxicity in these cell lines, was tested. Microarray analysis was performed to identify significant differentially expressed genes (DEGs) irrespective of APAP treatment. Genes up-regulated in BNL SV A.8 cells were associated with immune response, defense response, and apoptosis, while down-regulated genes were associated with catalytic activity, cell adhesion and the cytochrome P450 family. Consistent with the cytotoxicity data, no significant DEGs were found in BNL CL.2 cells after treatment with $625{\mu}M$ APAP, while cell cycle arrest and apoptosis-related genes were up-regulated in BNL SV A.8 cells. Based on the significant fold-changes in their expression, a genes were selected and their expressions were confirmed by quantitative real-time RT-PCR; there was a high correlation between them. These results suggest that gene expression profiles may provide a useful method for evaluating drug sensitivity of cell lines and eliciting the underlying molecular mechanism. We further compared the genes identified from our current in vitro studies to the genes previously identified in our lab as regulated by APAP in both C57BL/6 and ICR mice in vivo. We found that a few genes are regulated in a similar pattern both in vivo and in vitro. These genes might be useful to develop as in vitro biomarkers for predicting in vivo hepatotoxicity. Based on our results, we suggest that gene expression profiles may provide useful information for elucidating the underlying molecular mechanisms of drug susceptibility and for evaluating drug sensitivity in vitro for extrapolation to in vivo.
Koo, Hwa Seon;Cha, Sun Hwa;Kim, Hye Ok;Song, In Ok;Min, Eung Gi;Yang, Kwang Moon;Park, Chan Woo
Clinical and Experimental Reproductive Medicine
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v.42
no.4
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pp.149-155
/
2015
Objective: The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. Methods: This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. Results: The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group ($17.3{\pm}7.2$ vs. $11.0{\pm}7.2$; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. Conclusion: Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer.
Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression.
Atractylis lancea (Thunb.) DC. (AL), an important medicinal herb in Asia, has been shown to have anti-tumor effects on cancer cells, but the involved mechanisms are poorly understood. This study focused on potential effects and molecular mechanisms of AL on the proliferation of the Hep-G2 liver cancer cell line in vitro. Cell viability was assessed by MTT test in Hep-G2 cells incubated with an ethanol extract of AL. Then, the effects of AL on apoptosis and cell cycle progression were determined by flow cytometry. Telomeric repeat amplification protocol (TRAP) assays was performed to investigate telomerase activity. The mRNA and protein expression of human telomerase reverse transcriptase (hTERT) and c-myc were determined by real-time RT-PCR and Western blotting. Our results show that AL effectively inhibits proliferation in Hep-G2 cells in a concentrationand time-dependent manner. When Hep-G2 cells were treated with AL after 48h,the $IC_{50}$ was about 72.1 ${\mu}g/mL$. Apoptosis was induced by AL via arresting the cells in the G1 phase. Furthermore, AL effectively reduced telomerase activity through inhibition of mRNA and protein expression of hTERT and c-myc. Hence, these data demonstrate that AL exerts anti-proliferative effects in Hep-G2 cells via down-regulation of the c-myc/hTERT/telomerase pathway.
In order to estimate energy budget of the rockfish, Sebastes schlegeli juvenile, during the period from parturition to juvenile, of rockfish were reared at constant condition of water temperature($16^{\circ}C$ and $20^{\circ}C$). Energy used by the reared juveniles were calculated from estimates of data on growth, oxygen consumption, nitrogen excretion, feeding and energy content. After parturition, total length of juvenile was 4.56~5.49mm(average 4.97mm, n=20), and the average dally growth rates were 0.50mm at $20^{\circ}C$. The weight-specific oxygen consumption and nitrogen excretion rates decreased with increasing body weight. Temperature significantly affected oxygen consumption and nitrogen execretion rates, with the higher rates at $20^{\circ}C$ than $16^{\circ}C$. During the 25 days from parturition to jllveniles, feeding rates were 65.8cal at $16^{\circ}C$, and 89.2cal at $20^{\circ}C$. The assimilation effeciency estimated by nitrogen content of food and egested feces were 85.21% at $16^{\circ}C$ and $20^{\circ}C$. During the period from parturition to juvenile, energy was used the higher in body growth than in oxygen consumption. The gross growth efficiencies($K_1$)and net growth efficiencies($K_2$) of the rockfish, Sebastes schlegeli juvenile ranged from 43% to 47% and from 50% to 55%, respectively.
Journal of the Korean Society of Clothing and Textiles
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v.36
no.9
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pp.901-915
/
2012
This study comparatively analyzes the characteristics, changes, and differences in class-based costume typology according to a concept of $17^{th}$ and $18^{th}$ century common people in France. The methods and contents are as follow. First, the scope of common people is grasped according to the historical background and a concept of $17^{th}$ and $18^{th}$ century common people in France. Second, through considering a prior research on analyzing the data of ancient documents on the economy of clothing, it classifies common people into bourgeoisie, urban common people, rural common people, and the destitute. It then examines diachronic evolution, and class-based synchronic difference in the consumption of $17^{th}$ and $18^{th}$ century common people's costumes in France. Third, it analyzes the appearance frequency by period according to type of common people's costumes, which were shown in pictorial materials with 283 sheets of engravings and 54 pieces of paintings; in addition, it reconstructs the succession and expansion in typology. It grasps differences and changes in morphology by class, space, and period of typology for common people's costumes. Common people's consumption of costumes was understood to have grown in qualitative aspects as well as a rise in the whole clothing demand. A class-based structure formed and indicated that a fashion cycle existed. As a result of analyzing common people's clothes (shown in pictorial materials of the $17^{th}$ and $18^{th}$ century) 41 items were grasped by gender and according to costume kind. Typology in common people's costumes (classified into bourgeoisie, urban common people, rural common people, and the destitute) showed a change by period. A change in typical costume typology was accepted more by the bourgeoisie than by urban and rural common people, and was accepted more by rural communities than by urban populations. Thus, a difference was formed through an expansion with a temporal difference that depended on class and space.
Kim, Chung-Hoon;Ahn, Jun-Woo;Moon, Jei-Won;Kim, Sung-Hoon;Chae, Hee-Dong;Kang, Byung-Moon
Development and Reproduction
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v.18
no.3
/
pp.145-152
/
2014
This study was performed to investigate the effect of of transdermal testosterone gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian morphology according to pretreatment duration in poor responders. A total of 120 women were recruited for this pilot study. They were randomized into control, 2 weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups, 12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period of study stimulation cycle. After 3 weeks of TTG pretreatment, significant increase of antral follicle count (AFC) and significant decreases of mean follicular diameter (MFD) and resistance index (RI) value of ovarian stromal artery were observed (p=0.026, p<0.001, p<0.01, respectively). The total dose of rhFSH administered for COS significantly decreased after 3 and 4 weeks TTG treatment both compared with control group (p<0.001, p<0.001). The numbers of oocytes retrieved and mature oocytes were significanty higher in 3 and 4 weeks TTG treatment groups than control group (p<0.001, p<0.001 in the number of oocytes retrieved; p<0.001, p<0.001 in the number of mature oocytes). The clinical pregnancy rate and live birth rate were increased only in 4 weeks TTG treatment group compared with control group (p=0.030 and p=0.042, respectively). These data demonstrated that TTG pretreatment for 3 to 4 weeks increases AFC and ovarian stromal blood flow, thereby potentially improving the ovarian response to COS and IVF outcome in poor responders undergoing IVF/ICSI.
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