Baicalein, a bioactive flavonoid, has poor water solubility, thereby limiting its use in a wide range of biological applications. In the present study, we used inclusion complexes of cysteinyl ...β‐cyclodextrin (β‐CD) with baicalein to enhance the stability and solubility of baicalein in aqueous solution. We examined the effects of inclusion complexes of cysteinyl β‐CD on collagen synthesis following ultraviolet (UV) irradiation, as well as the mechanisms underlying its effects. Our findings demonstrated that baicalein significantly restored collagen synthesis in the UV‐exposed human fibroblast Hs68 cells. In addition, synthetic cysteine functionalized β‐CDs were found to promote baicalein‐induced collagen synthesis. Inclusion complexes of cysteinyl β‐CDs with baicalein significantly upregulated the protein expression of type I collagen and activated the transcription of type I, II, and III collagen. Inclusion complexes of cysteinyl β‐CDs with baicalein also downregulated matrix metalloproteinase ‐1 and ‐3, and α‐smooth muscle actin expression. In addition, inclusion complexes of cysteinyl β‐CDs with baicalein attenuated the expression of caveolin‐1, but this treatment enhanced the UV‐induced phosphorylation of Smad in the transforming growth factor‐β pathway. These results suggested that the newly synthesized derivative of CD can be used as a complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis.
We show that newly synthesized derivative of cysteinyl β‐cyclodextrin can be used as complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis in ultraviolet‐exposed human fibroblast Hs68 cells.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Significant increases in cell density and product titer have led to renewed interest in the application of depth filtration for initial clarification of cell culture fluid in antibody production. The ...performance of these depth filters will depend on the local pressure and velocity distribution within the filter capsule, but these are very difficult to probe experimentally, leading to challenges in both process design and scale‐up. We have used a combination of carefully designed experimental studies and computational fluid dynamics (CFD) to examine these issues in both lab‐scale (SupracapTM 50) and pilot‐scale (StaxTM) depth filter modules, both employing dual‐layer lenticular PDH4 media containing diatomaceous earth. The SupracapTM 50 showed a more rapid increase in transmembrane pressure and a more rapid DNA breakthrough during filtration of a Chinese Hamster Ovary cell culture fluid. These results were explained using CFD calculations which showed very different flow distributions within the modules. CFD predictions were further validated using measurements of the residence time distribution and dye binding in both the lab‐scale and pilot‐plant modules. These results provide important insights into the factors controlling the performance and scale‐up of these commercially important depth filters as well as a framework that can be broadly applied to develop more effective depth filters and depth filtration processes.
The authors evaluated the performance characteristics for both lab‐and pilot‐scale depth filtration modules for Chinese Hamster Ovary (CHO) cell clarification. The pilot‐scale module showed greater capacity and DNA removal due to more uniform flow distribution, which was verified by computational fluid dynamics, residence time distribution, and dye‐binding studies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Improved methods for predicting chemoresponsiveness involving the identification of polymorphic markers is highly desirable, considering narrow therapeutic index and frequent resistance to ...anti‐cancer regimens. The genome‐wide screening of chemosensitive single nucleotide polymorphisms (SNPs) was undertaken in association with in vitro chemosensitivity assays in 104 colorectal cancer patients for the initial screening step. Allele frequency, linkage disequilibrium, potential function, and Hardy–Weinberg equilibrium of the candidate SNPs were then determined for the identifying step. Finally, clinical association analysis in the other 260 evaluable patients or cell viability assays of transfected RKO cells was used to verify candidate SNPs for the validation step. In total, 12 SNPs to six regimens were initially chosen during the screening and identifying steps. In patients receiving fluoropyrimidine‐based adjuvant chemotherapy, the substitution alleles of GPC5 rs553717 (AA) correlated significantly with tumor recurrence and shorter disease‐free survival (P = 0.019 and 0.023, respectively). Interestingly, RKO cells expressing mutant GPC5 showed enhanced cell death in response to 5‐FU in cytotoxicity assays. Patients that were homozygous for the reference alleles SSTR4 rs2567608 (AA) and EPHA7 rs2278107 (TT) showed lower disease control rates in response to irinotecan and oxaliplatin regimens, respectively, than those with substitution alleles (P = 0.022 and 0.014, respectively). Thus, we identified chemosensitive SNP markers using a novel three step process of genome‐wide analysis consisting of in vitro screening, identification, and validation. The candidate chemosensitive SNP markers identified in our study, including those identified in vitro, can now be further verified in a large cohort study.
(Cancer Sci 2010; 101: 1007–1013)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and aims This study was to evaluate the efficacy of histone deacetylase (HDAC) inhibitors in colorectal cancer together with other established regimens. Materials and methods ...Chemosensitivities of 114 colorectal cancer patients to established regimens (fluorouracil (5-FU with leucovorin (FL), capecitabine, FL with irinotecan (FLIRI), and FL with oxaliplatin (FLOX)) as well as five hydroxamic acid derivatives (suberoylanilide hydroxamic acid, PXD101, and three novel candidates of CG-1, CG-2, and CG-3) were comparatively evaluated using the histoculture drug response assay. Results The chemosensitivity with established regimens was between 34.2% and 52.6%, when the cutoff value of the inhibition ratio was set at 30%, and between 54.5% and 84.1% with HDAC inhibitors. All HDAC inhibitors displayed synergistic effects in combination with established regimens of FLOX and FLIRI (P <= 0.0001-0.002). Advanced T- and N-category tumors and patients with synchronous adenoma displayed higher chemosensitivity to CG-3, CG-2, and CG-1, respectively, on a multivariate analysis (P = 0.023, 0.044, and 0.045, respectively). Tumors with mismatch repair defects were closely correlated with chemosensitivities to combined regimens of PDX101 with FLOX and FLIRI (P = 0.044 and 0.048, respectively). Conclusions Our findings firstly demonstrated the chemo-responsiveness of colorectal cancers to HDAC inhibitors with therapeutic efficacy comparable to the established regimens. Additionally, tumor growth and heredity were significantly associated with specific regimens, supporting their possible role as chemosensitive predictors.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Activation of bypass signals such as MET and AXL has been identified as one of possible resistant mechanisms to EGFR-TKI. Since various oncoproteins are dependent on HSP90 for its maturation ...and stability, we investigated the effect of AUY922, a newly developed HSP90 inhibitor of non-geldanamycin class, in lung cancer cells with MET- and AXL-mediated resistance. We established resistant cell lines with HCC827 harboring the deletion mutation on exon 19 of EGFR gene by long-term exposure to increasing concentrations of gefitnib and erlotinib (designated as HCC827/GR and HCC827/ER, respectively). The resistance of HCC827/GR was mediated by MET activation, whereas AXL activation caused resistance in HCC827/ER. AUY-922 treatment effectively suppressed the proliferation and induced cell death in both resistant cell lines. Accordingly, down-regulation of MET and AXL leading to decreased activation of Akt was noted. The inhibitory effect of AUY-922 on AXL and MET was also confirmed in AXL or MET-transfected LK-2 cells. In addition, AUY-922 led to reduced capability of invasion and migration of resistant cells. AUY-922 was effective to control the tumor growth in xenograft mouse models of HCC827/GR and HCC827/ER. Our study showed AUY-922 is one of promising therapeutic options for the MET- and AXL-mediated resistance to EGFR-TKI in lung cancer.
Citation Format: Jin Kyung Rho, Yun Jung Choi, Seon Ye Kime, Gwang Sup So, Se Hoon Choi, Chang-Min Choi, Jae Cheol Lee. A HSP90 inhibitor, AUY922, is effective to overcome the MET- and AXL-mediated resistance to EGFR-TKI in lung cancer. abstract. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1837. doi:10.1158/1538-7445.AM2014-1837
Objective:
Involvement of the parathyroid glands by metastatic tumor is rare. Breast is 1 of the primary sites in metastatic cancers. We introduce a rare case of metastatic breast carcinoma affecting ...a parathyroid gland, which was clinically combined with parathyroid gland hyperplasia.
Case Report:
A 65-year-old woman was referred due to hypercalcemia and constipation. The patient had a history of left breast carcinoma. She was admitted to the hospital because of the recent discovery of hypercalcemia and elevation of PTH. A Tc99m-sestamibi scan showed retained uptake in the right thyroid and in the lower pole of the left thyroid gland. Aspiration biopsy results revealed that the nodule in the posterior portion of the right thyroid was metastatic breast cancer and the nodule in the left thyroid gland was the hyperplastic parathyroid gland.
Conclusion:
This case illustrates that hyperparathyroidism caused by parathyroid hyperplasia was concurrent with metastatic breast cancer to a parathyroid gland without disseminated systemic metastasis. Although this case is very uncommon and it is not clear whether there is a relationship between breast cancer and primary hyperparathyroidism, that possibility should always be considered as the cause of hypercalcemia in patients with breast cancer.
•The physical and electrical effects by interfacial reactions of HfO2/Si/GaAs were investigated.•The results showed that the Si layer decreases the diffusion and formation of GaO.•The ...post-nitridation in HfO2/Si/GaAs significantly reduced the formation of AsO and GaO.•The Si passivation suppressed the interfacial defects caused by GaO and AsO diffusion.
The physical and electrical effects caused by interfacial reactions of HfO2 on Si-passivated GaAs were investigated by various methods. The results showed that the Si layer decreases the diffusion and formation of GaO. Moreover, post-nitridation in HfO2/Si/GaAs significantly reduced the formation of AsO and GaO. The depth profiling data showed that two separated layered structures were formed with HfO2 and a mixture of HfO2 and SiO2 after the annealing process. The crystalline structure and formation of GaO in the film affect the band offsets between GaAs and the high-k HfO2 dielectric. Moreover, the Si passivation effectively suppressed the interfacial defects caused by GaO diffusion during the annealing treatment. The nitridation cause As diffusion to oxygen vacancy of HfO2 result in the increase of the interfacial defect.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sulforaphane (SFN), a natural compound extracted from cruciferous vegetables, exhibits potent anticancer activity in various types of tumor cells. However, the effect of SFN on the proliferation of ...chondrocytes is not well understood. In the present study, we addressed the mechanism of action by which SFN suppresses proliferation. We demonstrate that SFN causes an irreversible arrest in cell proliferation, as determined by trypan blue dye exclusion assay and flow cytometric analysis. SFN induced cell cycle arrest at the G2/M phase by downregulation of cyclin B, cdc2 and cdc25c and upregulation of p21WAF1/CIP1 and p53 in a dose- and time-dependent manner, as determined by western blot analysis. Our data suggest that SFN regulates cell cycle arrest at the G2/M phase in rabbit articular chondrocytes.
Densely populated, vertically aligned carbon nanotubes (CNTs) grown by using thermal chemical
vapor deposition showed poor eld emission characteristics. An adhesive tape was rolled down on the
CNT ...layer and then peeled o, which decreased the CNT density by three orders of magnitude. The
tape treatment lowered the electric elds to emit 1 mA/cm2 from 5.4 to 3.9 V/m and improved
the emission image from spotty to uniform luminescence. The taped-o CNTs produced a very
high current density of 33.6 mA/cm2 at 6.7 V/m from an area of 1 1 cm2. Long-term emission
stability of CNTs was also considerably enhanced by the treatment. KCI Citation Count: 8
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
It is possible that hydrogen could replace coal and petroleum as the predominant energy source in the near future, but several challenges including cost, efficiency, and stability. Mg and Mg alloys ...are attractive hydrogen storage materials because of their lightweight and high absorption capacity. Their range of applications could be further extended if their hydrogenation properties could be improved. The main emphasis of this study was to investigate their hydrogenation properties for Synthesis of 10wt.% CaF2 in Mg2NiHx systems. The effect of BCR (66:1) and MA time (96 hours) on the hydrogenation properties of the composite was investigated. also, Mg2NiHx-10wt% CaF2 composites prepared by Mechanical Alloying are used in this work to illustrate the effect of catalysts on activation energy and kinetics of Magnesium hydride. KCI Citation Count: 2
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