Background: To investigate the inhibitory effect and the underlying mechanism of triptolide on cultured human endometrial carcinoma HEC-1B cells and corresponding xenograft. Materials and Methods: For in vitro studies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cell cycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivo studies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, then the tumor-bearing mice were treated with high, medium, and low-dose ($8{\mu}g$, $4{\mu}g$ and $2{\mu}g/day$) triptolide or cisplatin at $40{\mu}g/day$ or normal saline as control. The mice were treated for 10-15 days, during which body weight of the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growth factor (VEGF) was analyzed by SABC immunohistochemistry. Results: Cell growth was significantly inhibited by triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated that triptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed that low concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higher concentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosis of the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%); high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared to normal saline control (P<0.05). Conclusions: triptolide inhibits HEC-1B cell growth both in vitro and in mouse xenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involve induction of tumor cell apoptosis and inhibition of tumor angiogenesis.
Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.
Kim, Keun-Young;Lim, Kyung-Min;Shin, Jung-Hun;Noh, Ji-Yoon;Ahn, Jae-Bum;Lee, Da-Hye;Chung, Jin-Ho
Toxicological Research
/
v.25
no.4
/
pp.175-180
/
2009
Lead (Pb) is a ubiquitously occurring environmental heavy metal which is widely used in industry and human life. Possibly due to a global industrial expansion, recent studies have revealed the prevalent human exposure to Pb and increased risk of Pb toxicity. Once ingested by human, 95% of absorbed Pb is accumulated into erythrocytes and erythrocytes are known to be a prime target for Pb toxicity. Most of the studies were however, focused on $Pb^{2+}$ whereas the effects of $Pb^{4+}$, another major form of Pb on erythrocytes are poorly understood yet. In this study, we investigated and compared the effects of $Pb^{4+}$, $Pb^{2+}$ and other heavy metals on procoagulant activation of erythrocytes, an important factor for the participation of erythrocytes in thrombotic events in an effort to address the cardiovascular toxicity of $Pb^{4+}$. Freshly isolated erythrocytes from human were incubated with $Pb^{4+}$, $Pb^{2+}$, $Cd^{2+}$ and $Ag^+$ and the exposure of phosphatidylserine (PS), key marker for procoagulant activation was measured using flow cytometry. As a result, while $Cd^{2+}$ and $Ag^+$ did not affect PS exposure, $Pb^{4+}$ and $Pb^{2+}$ induced significantly PS exposure in a dose-dependent manner. Of a particular note, $Pb^{4+}$ induced PS exposure with a similar potency with $Pb^{2+}$. PS bearing microvesicle (MV), another important contributor to procoagulant activation was also generated by $Pb^{4+}$. These PS exposure and MV generation by $Pb^{4+}$ were well in line with the shape change of erythrocyte from normal discocytes to MV shedding echinocytes following $Pb^{4+}$ treatment. Meanwhile, nonspecific hemolysis was not observed suggesting the specificity of $Pb^{4+}$-induced PS exposure and MV generation. These results indicated that $Pb^{4+}$ could induce procoagulant activation of erythrocytes through PS exposure and MV generation, suggesting that $Pb^{4+}$ exposure might ultimately lead to increased thrombotic events.
We identified the echinostome metacercariae in Chinese mystery snails, Cipangopaludina chinensis malleata, from Xiengkhuang Province, Lao PDR with morphologies of adult worms recovered. Total 20 snails were examined with artificial digestion method and then the collected metacercariae were orally infected to a mouse and a rat. Adult worms recovered from experimental animals were observed with a light microscope and a SEM. The metacercariae were round, 125×123 ㎛ in average size, with a moderately thick cyst wall, collar spines distributed in the head collar and excretory granules in 2 canals of excretory tube. Adult flukes (3-week-old in a rat) were elongated, ventrally curved and 5.310×1.023 mm in average size. Head collar distinct, bearing 43 collar spines with 5 end group ones on each side. Oral sucker subterminal, prepharynx very short, pharynx well developed, and esophagus relatively short. Cirrus sac well developed, with a saccular seminal vesicle, and ventral sucker very large. Ovary round and on the median line of the body. Testes tandom and elongated. Eggs operculated, elliptical and 90×57 ㎛ in average size. In the SEM observation, the head crown prominent, with 43 collar spines resembled with horns of younger stag. Scale-like tegumental spines were densely distributed on the surface between the head collar and ventral sucker, and their densities were decreased posteriorly. Conclusively, the metacercariae detected in C. chinensis malleata from Lao PDR were identified as those of Echinostoma macrorchis based on the morphological characteristics of adult worms.
Wang, Jia-Ni;Xu, Li-Hua;Zeng, Wei-Gen;Hu, Pan;Rabkin, Samuel D.;Liu, Ren-Rin
Asian Pacific Journal of Cancer Prevention
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v.16
no.3
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pp.1241-1245
/
2015
Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.
Journal of Korean Society of Environmental Engineers
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v.29
no.8
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pp.909-914
/
2007
Fluorine compounds are the essential chemicals for wet processes of semiconductor and LCD production line. Problems of conventional treatments for fluoride wastewater are their high operation costs and low fluoride removal capacity. In this study, cement paste containing various Ca-bearing hydrates such as portlandite, calcium silicate hydrate(CSH), and ettringite was investigated for fluoride removal. The objectives of this study are to assess the feasibility of using cement paste cured mixture of cement and water as an alternative agent for treatment of fluoride wastewater and to investigate fluoride removal capacity of the cement paste. The performance of cement paste was comparable to that of lime in the kinetic test. In column experiment where the effluent fluoride concentrations were below 0.5 mg/L. Then the leached calcium reached the maximum level of 800 mg/L. The nitrate reduced to the level of less than 10 mg/L. Nitrate in the wastewater was exchanged with interlayer sulfate of these cement hydrate LDHs. Phosphate concentration could be reduced to 10 mg/L by forming calcium phosphate. These results indicate that the cement paste generally has advantageous characteristics as an economical and viable substitute for lime to remove fluoride.
The slime, deposited in the bored pile due to falling soil particle, reduces the bearing capacity of bored pile and thus the stability of construction also decreases. The weight pendulum and iron have been used for estimating the slime thickness based on the subjective judgment and thus the previous method has a limitation of reliability. The objective of this paper is to suggest the method for estimating the slime thickness by using characteristics of electrical resistivity as scientific method. The temperature-compensation resistivity probe (TRP), which has a conical shape and the diameter of 35.7mm, is applied to the measurement of the electrical resistivity in the borehole during penetration. The field tests are carried out for estimating the slime thickness in the application site of bored pile. The slime thickness is calculated through the difference between excavation depth of borehole and measured data. Furthermore, the laboratory tests are also conducted for investigating effects of casing, time elapsing and relative density by using the specimen of slime. The laboratory test supporting the suggested method is reasonable for determining the slime depth. The paper suggests that the electrical resistivity method may be a useful method for detecting slime thickness and the method is expected to be applicable to various sites of bored piles.
Ji, Younghwan;Kim, Kihwan;Kim, Sungho;Hwang, Yeongcheol;Lee, Seungho
Journal of the Korean GEO-environmental Society
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v.11
no.12
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pp.47-56
/
2010
The construction of new roads and the consistent extension of already-existing roads or the line-shape revision of those roads are increased with the governmental investment to SOC facilities currently. Accordingly, the road cut slopes are in the trend of rapidly increasing. As the road slope has increased, a lot of human and property damages has entailed consequently and in the local case, numerous studies have carried out aiming at minimizing this damages caused by the rockfall and landslide. In general, standard falling rock prevention facility has employed for most of the local road slope based on "Guide for Installation and Management of Road Safety Facilities" published by MLTM(the Ministry of Land, Transport, and Maritime Affairs) but profound doubt has raised as to whether this rockfall prevention facility would function properly enough to prevent rockfall efficiently without any damages in case of actual occurrence of rockfall. In addition, it is a reality that in most cases, such work is relied on overseas technology as a whole as the local technical level is low and in case of rockfall prevention net, it is judged that a study on rockfall prevention net that is able to endure more powerful rockfall energy is required as the problem including net bursting is taken place as a result of enough bearing force being failed to be demonstrated due to its partial weak point(not uniformly made). Under this background, in this study, three kinds of model depending on mesh size of expanded metal that is considered to have an adoptability as rockfall prevention net, as target are selected and characteristics depending on mesh size of expanded metal is intended to be researched through a pull-out test performance by using pull-out test equipment rockfall prevention net.
Korean Journal of Construction Engineering and Management
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v.13
no.1
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pp.118-128
/
2012
As the bearing wall structure, which has been widely applied to domestic apartment buildings since the 1980s, cause many problems during remodeling of buildings, the government encourages constructors to adopt flat plate or rahmen structure through legal incentives. In line with such a trend, the green frame, an eco-friendly rahmen structure that has removed the shortcomings of previous structures, was developed to enhance structural safety, constructability, and eco-friendliness. The construction of green frame can reduce the labor cost and facilitate the composition of iron bars to reduce rebar loss through calculating the quality and establishing the bar bending schedule automatically on the precast concrete member data collected over the design phase. Therefore, the purpose of this study is to develop the algorithm to automate the calculation of iron bar volume for the green frame designed on composite precast concrete members. Automated algorithm to calculate concrete structural design information and design information. Practices through the application site should prove efficacy. The database established by the developed algorithm will automate the establishment of iron bar processing map and bar cutting list and the calculation of optimal composition and order volume to minimize the rebar loss. This will also reduce the expenses on management staff and overall construction cost through the minimization of rebar loss.
Journal of the Korean Society of Food Science and Nutrition
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v.44
no.4
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pp.516-523
/
2015
This study investigated the antimutagenic and anticancer effects of Platycodon grandiflorum extract (PGE) and its fractions against carcinogenic N-nitrosodimethylamine (NDMA) and genotoxicity. The Ames Salmonella mutagenicity test employing histidine mutants of Salmonella Typhimurium TA98 and TA100 was used to examine the mutagenicity of PGE and its fractions. Bacterial reversion assay with S. Typhimurium TA98 and TA100 did not show a significantly increased number of revertant colonies. The same test was used to examine the ability of PGE and its fractions to prevent acquisition of N-methyl-N'-nitro-N-nitrosoguanidine- and 4-introquino-line-1-oxide-induced mutations. PGE and its fractions inhibited mutagenesis in a dose-dependent manner. Among the fractions, ethyl acetate fraction from PGE (PGEA) exhibited a higher antimutagenic effect than other fractions. PGE and its fractions suppressed the growth of cancer cell lines, including human cervical adenocarcinoma, human hepatocellular carcinoma, human breast adenocarcinoma, human lung carcinoma, and transformed primary human embryonic kidney cells. In addition, we evaluated the antitumor activity of PGEA and its fractions in sacorma-180 solid tumor-bearing mice. In vivo anticancer activity results showed that PGE and its fractions could more effectively suppress tumor growth than the control. PGEA showed higher in vitro and in vivo anticancer effects than PGE and other fractions, and PGEA inhibited NDMA formation. Thus, we showed that PGEA has antimutagenic and anticancer activities, making it a candidate anticancer material under these experimental conditions.
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