683 research outputs found
Substitution of Heavy Complementarity Determining Region 3 (CDR-H3) Residues Can Synergistically Enhance Functional Activity of Antibody and Its Binding Affinity to HER2 Antigen
To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their anti-proliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity (IC50: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity (K-D : 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCI-N82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.OAIID:RECH_ACHV_DSTSH_NO:T201620640RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A002901CITE_RATE:2.67DEPT_NM:화학생물공학부EMAIL:[email protected]_YN:YCONFIRM:
Effects of a Tumor Necrosis Factor-α Antagonist on Experimentally Induced Rhinosinusitis
This prospective, randomized, and controlled study examined the effects of tumor necrosis factor soluble receptor type I (sTNFRI, a TNF-α antagonist) on experimentally induced rhinosinusitis in rats. The experimental groups received an instillation of lipopolysaccharide (LPS) plus an intramuscular injection of amoxicillin/clavulanate (antibiotic group), an instillation of sTNFRI (sTNFRI group), an instillation of sTNFRI and an injection of amoxicillin/clavulanate (sTNFRI/antibiotic group), or no additional treatment (LPS group). Histopathological changes were determined using hematoxylin-eosin and periodic acid-Schiff (PAS) staining. Leakage of exudate was determined using fluorescence microscopy. Vascular permeability was measured using the Evans blue dye technique. Expression of MUC5AC was measured using reverse transcriptase PCR. The sTNFRI, antibiotic, and sTNFRI/antibiotic groups had significantly less capillary permeability, mucosal edema, PAS staining, and expression of MUC5AC than the LPS group. There were no differences in capillary permeability, mucosal edema, PAS staining, and MUC5AC expression between the sTNFRI and sTNFRI/antibiotic groups. The antibiotic group had PAS staining similar to that of the sTNFRI and sTNFRI/antibiotic groups but had a greater increase in capillary permeability, mucosal edema, and MUC5AC expression. This study shows that sTNFRI reduces inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats
Association of Poor Differentiation or Positive Vertical Margin with Residual Disease in Patients with Subsequent Colectomy after Complete Macroscopic Endoscopic Resection of Early Colorectal Cancer
Monoclinic and Correlated Metal Phase in VO_2 as Evidence of the Mott Transition: Coherent Phonon Analysis
In femtosecond pump-probe measurements, the appearance of coherent phonon
oscillations at 4.5 THz and 6.0 THz indicating the rutile metal phase of VO_2
does not occur simultaneously with the first-order metal-insulator transition
(MIT) near 68^oC. The monoclinic and correlated metal(MCM) phase between the
MIT and the structural phase transition (SPT) is generated by a photo-assisted
hole excitation which is evidence of the Mott transition. The SPT between the
MCM phase and the rutile metal phase occurs due to subsequent Joule heating.
The MCM phase can be regarded as an intermediate non-equilibrium state.Comment: 4 pages, 2 figure
Multiple Epidermoid Cysts Arising from the Extratesticular Scrotal, Spermatic Cord and Perineal Area
An extratesticular scrotal epidermoid cyst is a relatively very rare condition, and an epidermoid cyst arising from the spermatic cord area is extremely rare. We report a case of multiple epidermoid cysts arising from the extratesticular scrotum, spermatic cord, and lower extremities. To our best knowledge, concomitant occurrence of these lesions has not been reported previously in the literature
CVD-grown monolayer MoS2 in bioabsorbable electronics and biosensors
Transient electronics entails the capability of electronic components to dissolve or reabsorb in a controlled manner when used in biomedical implants. Here, the authors perform a systematic study of the processes of hydrolysis, bioabsorption, cytotoxicity and immunological biocompatibility of monolayer MoS2
Insecticidal activities of a Diospyros kaki root-isolated constituent and its derivatives against Nilaparvata lugens and Laodelphax striatellus
a b s t r a c t a r t i c l e i n f o Diospyros kaki root-derived materials were examined for insecticidal properties against Nilaparvata lugens and Laodelphax striatellus. Based on the LD 50 values, the chloroform fraction of D. kaki extracts showed the most activity against N. lugens (3.78 μg/female) and L. striatellus (7.32 μg/female). The active constituent of the chloroform fraction was isolated by various chromatographic methods and was identified as 5-hydroxy-2-methyl-1,4-naphthoquinone by spectroscopic analyses. To establish the structure-activity relationships, the insecticidal effects of 5-hydroxy-2-methyl-1,4-naphthoquinone and its derivatives against N. lugens and L. striatellus were determined using micro-topical application bioassays. On the basis of LD 50 values, 5-hydroxy-1,4-naphthoquinone was the most effective against N. lugens (0.072 μg/female) and L. striatellus (0.183 μg/ female). 2-Bromo-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone, and 5-hydroxy-2-methyl-1,4-naphthoquinone also had potent insecticidal activities against N. lugens and L. striatellus. In contrast, no insecticidal activity was observed with 2-methoxy-1,4-naphthoquinone or 2-methyl-1,4-naphthoquinone. These results indicate that the functional group (bromo-and hydroxyl-) at the C-2 position of the 1,4-naphthoquinone skeleton and the change in position of the hydroxyl group play important roles in insecticidal activity. Therefore, naturally occurring D. kaki root-derived 5-hydroxy-2-methyl-1,4-naphthoquinone and its derivatives may be suitable as insecticides
Cystamine induces AIF-mediated apoptosis through glutathione depletion
AbstractCystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting γ-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death
Properties of Central Caustics in Planetary Microlensing
To maximize the number of planet detections, current microlensing follow-up
observations are focusing on high-magnification events which have a higher
chance of being perturbed by central caustics. In this paper, we investigate
the properties of central caustics and the perturbations induced by them. We
derive analytic expressions of the location, size, and shape of the central
caustic as a function of the star-planet separation, , and the planet/star
mass ratio, , under the planetary perturbative approximation and compare the
results with those based on numerical computations. While it has been known
that the size of the planetary caustic is \propto \sqrt{q}, we find from this
work that the dependence of the size of the central caustic on is linear,
i.e., \propto q, implying that the central caustic shrinks much more rapidly
with the decrease of compared to the planetary caustic. The central-caustic
size depends also on the star-planet separation. If the size of the caustic is
defined as the separation between the two cusps on the star-planet axis
(horizontal width), we find that the dependence of the central-caustic size on
the separation is \propto (s+1/s). While the size of the central caustic
depends both on and q, its shape defined as the vertical/horizontal width
ratio, R_c, is solely dependent on the planetary separation and we derive an
analytic relation between R_c and s. Due to the smaller size of the central
caustic combined with much more rapid decrease of its size with the decrease of
q, the effect of finite source size on the perturbation induced by the central
caustic is much more severe than the effect on the perturbation induced by the
planetary caustic. Abridged.Comment: 5 pages, 4 figures, ApJ accepte
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