• 제목/요약/키워드: Drug transport study

검색결과 69건 처리시간 0.027초

Genetic Variation in the ABCB1 Gene May Lead to mRNA Level Chabge: Application to Gastric Cancer Cases

  • Mansoori, Maryam;Golalipour, Masoud;Alizadeh, Shahriar;Jahangirerad, Ataollah;Khandozi, Seyed Reza;Fakharai, Habibollah;Shahbazi, Majid
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권18호
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    • pp.8467-8471
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    • 2016
  • Background: One of the major mechanisms for drug resistance is associated with altered anticancer drug transport, mediated by the human-adenosine triphosphate binding cassette (ABC) transporter superfamily proteins. The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy. In our study we have studied the possibility that structural single-nucleotide polymorphisms (SNP) are the mechanism of ABCB1 overexpression. Materials and Methods: A total of 101 gastric cancer multidrug resistant cases and 100 controls were genotyped with sequence-specific primed PCR (SSP-PCR). Gene expression was evaluated for 70 multidrug resistant cases and 54 controls by real time PCR. The correlation between the two groups was based on secondary structures of RNA predicted by bioinformatics tool. Results: The results of genotyping showed that among 3 studied SNPs, rs28381943 and rs2032586 had significant differences between patient and control groups but there were no differences in the two groups for C3435T. The results of real time PCR showed over-expression of ABCB1 when we compared our data with each of the genotypes in average mode. Prediction of secondary structures in the existence of 2 related SNPs (rs28381943 and rs2032586) showed that the amount of ${\Delta}G$ for original mRNA is higher than the amount of ${\Delta}G$ for the two mentioned SNPs. Conclusions: We have observed that 2 of our studied SNPs (rs283821943 and rs2032586) may elevate the expression of ABCB1 gene, through increase in mRNA stability, while this was not the case for C3435T.

부자(附子) "부타놀" 분획(分劃)이 심근(心筋) 수축단백(收縮蛋白)에 미치는 영향(影響) (Effect of Aconiti tuber butanol fraction on the contractile proteins of myocardium)

  • 양길성;박길수;박찬웅;임정규
    • 대한약리학회지
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    • 제12권1호
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    • pp.23-29
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    • 1976
  • 최근(最近) 현저한 심근수축증강작용(心筋收縮增强作用)이 알려져 있는 부자(附子) ${\ulcorner}$부타놀${\lrcorner}$ 분획의 작용기전(作用機轉)을 구명(究明)코저 하는 시도(試圖)의 일환으로 심근수축단백(心筋收縮蛋白)에 대한 직접적인 영향을 관찰하였다. 부자${\ulcorner}$부타놀${\lrcorner}$ 분획은 actomyosin ATPase 활성(活性)에 대하며 별(別) 영향을 미치지 않았으며 actin-myosin 상호결합(相互結合)에서 $Ca^{++}$과 유사한 역활을 나타내지도 못했다. 단 actomyosin의 superprecipitation에 대하여는 약간 촉진적(促進的)이었으나 이러한 작용은 actomyosin ATPase 활성(活性)의 증가를 동반치 못했다. 그러나 microsmal $Na^+-K^+$-activated ATPase 활성(活性)은 현저히 억제하였으며 이러한 현상은 부자(附子)${\ulcorner}$부타놀${\lrcorner}$ 분획이 $Ca^{++}$의 membrane transport에 영향을 미칠것으로 인정되는 사실로서 부자(附子)${\ulcorner}$부타놀${\lrcorner}$ 분획의 심근수축증강작용기전(心筋收縮增强作用機轉)의 일부는 근수축단백(筋收縮蛋白)에 대한 직접작용보다는 extracellular 또는 intracellular membrane에서의 $Ca^{++}$ 이동에 영향을 미쳐 세포내 유리 $Ca^{++}$농도를 증가시키는것이 간접적으로 심근수축(心筋收縮)을 촉진(促進)시킬 것으로 사료되었다.

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Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target

  • Saiki, Iwao;Yara, Miki;Yamanaka, Tsuyoshi;Uchino, Hiroyuki;Inazu, Masato
    • Biomolecules & Therapeutics
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    • 제28권2호
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    • pp.195-201
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    • 2020
  • Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [3H]Choline uptake was mediated by a single Na+-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [3H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [3H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.

푸드뱅크 기탁 조리식품의 미생물학적 위해분석 (II) (Microbiological Hazard Analysis of Cooked Foods Donated to Foodbank (II))

  • 박형수;류경
    • 대한영양사협회학술지
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    • 제13권4호
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    • pp.389-406
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    • 2007
  • This study was conducted to estimate the safety level of non-cooking and cooking processed foods to propose the sanitary management of foods donated to foodbanks. The time and temperature were measured and the microbial levels of aerobic plate counts (APC), coliforms, E. coli, Salmonella spp., S. aureus, B. cereus, and E. coli O157:H7 were analyzed on ten food items donated to seven foodbanks. The amount of cooked foods donated to each foodbank was about 10 to 40 servings. All foodbanks hired a supervisor and had at least one refrigerator/freezer and one temperature-controlled vehicle, but only four foodbanks had the separate offices to manage the foodbank operation. The flow of donated foods was gone through the steps; production, meal service and holding at donator, collection by foodbank, transport (or holding after transport) and distribution to recipients. After production, the levels of APC of both non-cooking and cooking processed foods were complied with the standards by Ministry of Education & Human Resources Development, and were not increased till distribution. Only the level of coliforms in dried squid & cucumber salad (1.5×$10^3$ CFU/g) was not met the standards. E. coli and other pathogens were not detected in all tested samples. The microbial levels of delivery vessels and work tables were satisfactory, but the APC levels of two of four tested serving tables (6.9×$10^3$ and 5.3×$10^3$ CFU/100$cm^2$) and the coliforms level of one (1.1×$10^3$ CFU/100$cm^2$) were over the standards. The air-borne microflora level in serving room was estimated as satisfactory. It took about 3.0 to 6.5 hours from after-production to distribution and the temperatures of donated foods were exposed mostly to temperature danger zone, which had a high potential of microbial growth. These results imply that a checklist to monitor time and temperature in each step should be provided and the employees involving foodbank operation should be properly educated to ensure the safety of donated foods.

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Industrialization possibilities of purified pig sperm hyaluronidase

  • Soojin Park;In-Soo Myeong;Gabbine Wee;Ekyune Kim
    • Journal of Animal Science and Technology
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    • 제65권6호
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    • pp.1205-1213
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    • 2023
  • The goals of the present study were to develop a simple method for obtain highly purified pig sperm hyaluronidase (pHyase) and to assess its activity, function, and safety. In mammals, sperm-specific glycophosphatidylinositol (GPI)-anchored Hyase assists sperm penetration through the cumulus mass surrounding the egg and aids in the dispersal of the cumulus-oocyte complex. Recently, Purified bovine sperm hyaluronidase (bHyase) has been shown to enhance therapeutic drug transport by breaking down the hyaluronan barrier to the lymphatic and capillary vessels, thereby facilitating tissue absorption. Commercially available Hyase is typically isolated from bovine or ovine; which have several disadvantages, including the risk of bovine spongiform encephalopathy, low homology with human Hyase, and the requirement for relatively complex isolation procedures. This study successfully isolated highly purified pHyase in only two steps, using ammonium sulfate precipitation and fast protein liquid chromatography. The isolated Hyase had activity equal to that of commercial bHyase, facilitated in vitro fertilization, and effectively dissolved high molecule hyaluronic acid. This simple, effective isolation method could improve the availability of pHyase for research and clinical applications.

난류유동장에서 Shear - thinning 유체에 의한 마찰저항 감소에 관한 연구 (A Study on the Drag Reduction by Shear-thinning Fluid in Turbulent Flow Fields)

  • 차경옥;김재근;오율권
    • Journal of Advanced Marine Engineering and Technology
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    • 제21권2호
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    • pp.126-135
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    • 1997
  • Drag reduction in polymer solutions is the phenomenon where by extremely dilute solutions of high molecular weight polymers exhibit frictional resistance to flow much lower than the pure solvent. This effect, largely unexplained as yet, has attracted the attention of polymer scientists and fluid flow specialists. Although applications are beginning to appear, the principle interest to data has been in attempting to relate the effect to the fluid mechanics of turbulent flow. Drag reduction in two phase flow can be applied to the transport of crude oil, phase change system such as chemical reactor, and pool and boiling flow. But the research on drag reduction in two phase flow is not intensively investigated. Therefore, experimental investigations have been carried out to analyze the drag reduction produced by polymer addition in the single phase and two phase flow system. The objectives of the proposed investigation are primarily in identifying and developing high performance polymer additives for fluid transportations with the benefits of turbulent drag. Also we want to is to evaluate the drag reduction in horizontal flow by measuring pressure drop and mean velocity. Experimental results show higher drag reduction using co - polymer(A611P) then using polyacrylamide (PAAM) and faster degradation using PAAM than using A611P under the same superficial velocity.

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비기허(脾氣虛)로 인한 내습(內濕)의 발생과 사군자탕(四君子湯) (Study on the Endogenous Dampness Caused by Gi Deficiency of the Spleen and Sagunja-tang)

  • 정한솔;하기태;신상우;이광규
    • 동의생리병리학회지
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    • 제24권6호
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    • pp.903-906
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    • 2010
  • The spleen is the source of gi, blood, body fluid and plays a vital role in maintaining life. The function of the spleen is to transform food nutrients and water, and to transport them to the heart and the lung. The movement of splenic gi is marked by elevation. The spleen governs the activity of elevating the lucid. The function of transportation and transformation is usually disturbed in the state of Gi deficiency of the spleen. The main clinical manifestations of gi deficiency of the spleen can be divided into as followers: anorexia, loose stool if the digesting and absorbing functions are disturbed; phlegm and edema if dampness and water are retained due to unhealthy water metabolism. Sagunja-tang can be applied for gi deficiency syndrome of the spleen. Ingredient bakchul(Rhizoma Atractylodis Macrocephalae) and bokryeung(Poria) can be used as monarch drug to eliminate dampness and strengthen the spleen.

Buccal Transport of Paclitaxel using Ethanol and Glyceryl Monooleate

  • Lee, Yoon-Jin;Kang, Myung-Joo;Park, Young-Mi;Choi, Young-Wook;Lee, Jae-Hwi
    • Journal of Pharmaceutical Investigation
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    • 제37권5호
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    • pp.311-314
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    • 2007
  • Paclitaxel (PTX) is an antineoplastic agent approved for the treatment of ovarian and breast carcinomas. However, the use of paclitaxel as an anticancer drug is limited by its extremely poor water solubility (below $0.3\;{\mu}g/mL$). Furthermore, it has very low bioavailability when administered orally because paclitaxel is a substrate of P-glycoprotein (P-gp) efflux pump. In this study, buccal delivery of PTX was investigated as one of the alternatives for PTX delivery. Ethanol and glyceryl monooleate (GMO) were selected as permeation enhancing agents to increase solubility and permeation across buccal mucosa of PTX. At the different concentrations of ethanol solution ($30{\sim}70\;w/w\;%$), PTX permeation was studied, followed effects of GMO in the concentration range of $2.5{\sim}25%$ with ethanol vesicle. The transbuccal ability of PTX was evaluated in vitro using Franz diffusion cells mounted with rabbit buccal mucosa. As a result, incorporation of PTX into ethanol vesicle with GMO significantly enhanced the PTX permeation in rabbit buccal mucosa. Particularly, the mixtures of ethanol:water:GMO at the ratio of 50:47.5:2.5 showed the most excellent enhancing ability. The results showed a promising possibility for buccal delivery of PTX.

Upregulation of Glutathion S-Transferase mu 1 in Bovine Cystic Follicles

  • Kang, Da-Won;Kim, Chang-Woon;Han, Jae-Hee
    • 한국수정란이식학회지
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    • 제25권4호
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    • pp.273-279
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    • 2010
  • Follicular cystic follicles (FCFs) show delayed regression with persistent follicle growth. However, the mechanism by which follicles are persistently grown remains unclear. Glutathione S-transferases (GSTs) are drug-metabolizing and detoxification enzymes that are involved in the intracellular transport and metabolism of steroid hormones. In this study, a proteomic analysis was performed to identify whether GST expression is changed in bovine FCFs and to predict the interactions between GST and other proteins. Normal follicles and FCFs were classified based on their sizes (5 to 10 mm and 25 mm). In bovine follicles, GST mu 1 (GSTM1) was detected as a differentially expressed protein (DEP) and significantly up-regulated in FCFs compared to normal follicles (p<0.05). Consistent with the proteomic results, semi-quantitative PCR data and western blot analysis revealed an up-regulation of GSTM1 in FCFs. Expression levels of aromatase and dehydrogenase proteins were changed in FCFs. These results show that the up-regulation of GSTM1 that is observed in bovine FCFs is likely to be responsible for the persistent follicle growth in FCFs as the activity of aromatase and the dehydrogenases.

Multivesicular Liposomes for Oral Delivery of Recombinant Human Epidermal Growth Factor

  • Li Hong;An Jun Hee;Park Jeong-Sook;Han Kun
    • Archives of Pharmacal Research
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    • 제28권8호
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    • pp.988-994
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    • 2005
  • The purpose of the present study was to prepare multivesicular liposomes with a high drug loading capacity and to investigate its potential applicability in the oral delivery of a peptide, human epidermal growth factor (rhEGF). The multivesicular liposomes containing rhEGF was prepared by a two-step water-in-oil-in-water double emulsification process. The loading efficiency was increased as rhEGF concentration increased from 1 to 5mg/mL, reaching approximately $60\%$ at 5 mg/mL. Approximately $47\%$ and $35\%$ of rhEGF was released from the multivesicular liposomes within 6 h in simulated intra-gastric fluid (pH 1.2) and intra-intestinal fluid (pH 7.4), respectively. rhEGF-loaded multivesicular liposomes markedly suppressed the enzymatic degradation of the peptide in an incubation with the Caco-2 cell homogenate. However, the transport of rhEGF from the multivesicular liposomes to the basolateral side of Caco­2 cells was two times lower than that of the rhEGF in aqueous solution. The gastric ulcer healing effect of rhEGF-loaded multivesicular liposomes was significantly enhanced compared with that of rhEGF in aqueous solution; the healing effect of the liposomes was comparable to that of the cimetidine in rats. Collectively, these results indicate that rhEGF-loaded multivesicular liposomes may be used as a new strategy for the development of an oral delivery system in the treatment of peptic ulcer diseases.