• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.411-416
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• 2017

Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than $1{\mu}g/mL$, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of ${\small{DL}}-{\alpha}$-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization. The HPNs were $85.2{\pm}7.55nm$ in diameter and had a zeta potential of $-35.7{\pm}0.25mV$. The encapsulation efficiency was almost 100%, and the PTX content was 3.0 mg/mL. We assessed the in vivo antitumor efficacy of the HPNs by measuring changes in tumor volume and body weight in nude mice transplanted with CD44-overexpressing NCI-H460 xenografts and treated with a bolus dose of saline, $Taxol^{(R)}$, PTX nanoemulsions (PNs), or HPNs at a dose of 25 mg/kg. Suppression of cancer cell growth was higher in the PN- and HPN-treated groups than in the $Taxol^{(R)}$ group. In particular, HPN treatment dramatically inhibited tumor growth, likely because of the specific tumor-targeting affinity of HA for CD44-overexpressed cancer cells. The loss of body weight and organ weight did not vary significantly between the groups. It is suggest that HPNs should be used to effective nanocarrier system for targeting delivery of non-small cell lung cancer overexpressing CD44 and high solubilization of poorly soluble drug.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5493-5498
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• 2014

Objective: To compare the efficacy of taxane-based regimens in the first line setting retrospectively in Chinese patients with recurrent and/or metastatic esophageal cancer. Methods: We analyzed 102 recurrent and/or metastatic esophageal cancer patients who received taxanes-based regimens in a first-line setting from January 2009 to December 2013. Sixteen (15.7%) patients were administered Nab-PTX based chemotherapy and 86 patients (84.3%) received paclitaxel (PTX) or docetaxel (DTX) based chemotherapy. Patients in the PTX/DTX group could be further divided into TP (71 patients) and TPF (15 patients) groups. Results: The objective response rate (ORR) of all patients was 20.6%, and the disease control rate (DCR) was 67.6%. The median overall survival (OS) was 10.5 months (95% CI 10.1-16.4) and the median progression-free survival (PFS) was 6.04 months (95% CI 5.09-7.91). The DCR was higher in the TPF group than the TP group (93.3% vs. 59.1%; p = 0.015 ). There were no significant differences in ORR, OS, and PFS among Nab-PTX, TPF and TP groups. Conclusions: The three regimens of Nab-PTX based, TP and TPF proved active in a first line setting of Chinese patients with recurrent and/or metastatic esophageal cancer, and should thus be regarded as alternative treatments.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.355-363
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• 1995

It has been well known that the intracellular calcium concentration $([Ca^{2+}]_i)$ in living cell is very sensitive to live or to survive, but the transmembrane system of calcium ion, especially mechanism of calcium ion movement in unexcitable state has been little elucidated. Though many proposed theories for calcium ion transport have been reported, it is still unclear that how could the sustained maintenance in cytosolic calcium level be done in cell. Since one of possible mechanisms of calcium transport may be related to the acetylcholine receptor-linked calcium channel, author performed experiment to elucidate this mechanism of calcium influx related to cholinergic receptor in ml muscarinic receptor-transfected RBL-2H3 cell-line. 1) The effects of carbachol both on calcium ion influx and on the secretion of hexosaminidase were respectively observed in the manner of time-related or concentration-dependent pattern in this model. 2) The effects of several metal cations on calcium transport were shown in carbachol-induced cell-line. 3) Atropine was administered to examine the relationship between cholinergic receptor and calcium ion influx in this model. 4) PMA (Phorbol 12-myristate 13-acetate) or PTx (Pertussis toxin) was respectively administered to examine the secondary mediator which involved pathway of calcium ion movement in carbachol-induced cell-line. The results of this experiments were as follows; 1) Carbachol significantly stimulated both the calcium influx and the secretion of hexosaminidase in the manner of the concentration-dependent pattern. 2) Atropine potently blocked the effects of carbachol in concentration-response manner. 3) Administered metal cations inhibited the calcium influx in carbachol-stimulated this model to the concentration-related pattern. 4) PMA did not inhibit carbachol-induced secretion of hexosaminidase, but blocked the calcium influx in this cell-line. 5) The suppression of carbachol-induced hexosaminidase secretion was shown in PTx-treated cell -line.

• Fisheries and Aquatic Sciences
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• v.1 no.2
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• pp.153-158
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• 1998

Effects of cyclic (c) AMP and G-protein related reagents (3-isobutyl-l-methyxanthine (IBMX), Forskolin (FSK), cholera toxin (CTX), and pertussis toxin (PTX≫ on estradiol-17$\beta$ induced vitellogenin (VTG) induction were examined in primary hepatocyte cultures in rainbow trout Oncorhynchus mykiss. The addition of IBMX, FSK, or CTX to the incubation medium markedly increased VTG production, while PTX was not effective in stimulating the production. It is well known that cAMP regulates phosphorylation and dephosphorylation through mediation of protein kinase A. These results suggest that VTG production is highly dependent on cAMP state in hepatocytes because of its highly phosphorylated nature.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.139-147
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• 2013

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at $10^{-6}M$ and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only $PKC{\varepsilon}$ antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-${\varepsilon}$ pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

• Animal cells and systems
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• v.14 no.3
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• pp.155-160
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• 2010

Extracellular signal-regulated kinases 1/2 (ERK1/2) play important roles in a variety of biological processes including cell growth and differentiation. We have previously reported that GAR-3 activates ERK1/2 via phospholipase C and protein kinase C, presumably through pertussis toxin (PTX)-insensitive Gq proteins, in Chinese hamster ovary (CHO) cells. Here we provide evidence that GAR-3 also activates ERK1/2 through PTX-sensitive G proteins, phosphatidylinositol 3-kinase (PI 3-kinase), and Src family kinases in CHO cells. We further show that in human embryonic kidney (HEK293) cells, epidermal growth factor receptor and Ras are required for efficient ERK1/2 activation by GAR-3. Taken together, our data indicate that GAR-3 evokes ERK1/2 activation through multiple signaling pathways in cultured mammalian cells.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.77.3-78
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• 2003

We previously shown that sphingosylphosphorylcholine, a lysophosphatidic acid, produced contraction in isolated single cells of cat ilium. We investigated the mechanism of sphingosine-1-phosphate (S1P)-induced contraction of circular smooth muscle cells in cat esophagus. S1P produced esophageal contraction in a dose dependent manner. The maximal contraction (l0$\^$-7/ M) induced at 1min. Pertusis toxin (PTX) inhibited contraction induced by S1P, suggesting that the contraction is mediated to a PTX-sensitive G-protein. (omitted)

• BMB Reports
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• v.40 no.5
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• pp.731-739
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• 2007

The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles.

• Korean Journal of Food Science and Technology
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• v.44 no.4
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• pp.390-392
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• 2012

Diarrhetic shellfish poisoning toxins were investigated by liquid chromatography-electrospray ionization mass spectrometry (LC-MS/MS). Okadaic acid (OA), Dinophysistoxin-1 (DTX1), Pectonotoxin2, (PTX2) and Yessotoxin (YTX) in bivalves were quantified. OA were found in four samples; mussel Mytilus edulis (0.001 ${\mu}g/g$), Oyster Crassostrea gigas (0.004 and 0.001 ${\mu}g/g$) and manila clam Ruditapes philippinarum (0.001 ${\mu}g/g$). DTX1, PTX2, and YTX were not detected from all of the samples examined.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7561-7568
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• 2013

Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be involved in cancer progression but its contribution to epithelial ovarian cancer (EOC) remains unclear. The present study sought to determine the role of Gal-3 in chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX) using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41% increased cell proliferation, 36% decreased caspase-3 activity and 33.6% increased substrate-dependent adhesion in the presence of rhGal-3 compared to the control case (p<0.001). Treatment of cells with a non-effective dose of PTX (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3 activity. Moreover, there was 39% decrease in substrate-dependent adhesion compared to control (p<0.001). These results suggest that inhibition of Gal-3 could be a useful therapeutic tool for combination therapy of ovarian cancer.