HMGN5 is a typical member of the HMGN (high mobility group nucleosome-binding protein) family which may function as a nucleosomal binding and transcriptional activating protein. Overexpression of HMGN5 has been observed in several human tumors but its role in tumorigenesis has not been fully clarified. To investigate its significance for human lung cancer progression, we successfully constructed a shRNA expression lentiviral vector in which sense and antisense sequences targeting the human HMGN5 were linked with a 9-nucleotide loop. Inhibitory effects of siRNA on endogenous HMGN5 gene expression and protein synthesis were demonstrated via real-time RT-PCR and western blotting. We found HMGN5 silencing to significantly inhibit A549 and H1299 cell proliferation assessed by MTT, BrdU incorporation and colony formation assays. Furthermore, flow cytometry analysis showed that specific knockdown of HMGN5 slowed down the cell cycle at the G0/G1 phase and decreased the populations of A549 and H1299 cells at the S and G2/M phases. Taken together, these results suggest that HMGN5 is directly involved in regulation cell proliferation in A549 and H1299 cells by influencing signaling pathways involved in cell cycle progression. Thus, our finding suggests that targeting HMGN5 may be an effective strategy for human lung cancer treatment.
Objective: To explore the relationships between primary tumor $^{18}F$-FDG uptake measured as the SUVmax and local extension, and nodal or distant organ metastasis in patients with NSCLC on pretreatment PET-CT. Methods: 93 patients with NSCLC who underwent $^{18}F$-FDG PET-CT scans before the treatment were included in the study. Primary tumor SUVmax was calculated; clinical stages, presence of local extension, nodal and distant organ metastases were recorded. The patients with SUVmax${\geq}2.5$ were divided into low and high SUVmax groups by using the median SUVmax. The low SUVmax group consisted of 45 patients with SUVmax<10.5, the high SUVmax group consisted of 46 patients with SUVmax${\geq}10.5$. Their data were compared statistically. Results: 91 cases with SUVmax${\geq}2.5$ were included for analysis. The mean SUVmax in patients without any metastasis was $7.42{\pm}2.91$ and this was significantly lower than that ($12.18{\pm}4.94$) in patients with nodal and/or distant organ metastasis (P=0.000). In the low SUV group, 19 patients had local extension, 22 had nodal metastasis, and 9 had distant organ metastasis. In the high SUV group, 31 patients had local extension, 37 had nodal metastasis, and 18 had distant organ metastases. There was a significant difference in local extension (P =0.016), distant organ metastasis (P =0.046), and most significant difference in nodal metastasis rate (P =0.002) between the two groups. In addition, there was a moderate correlation between SUVmax and tumor size (r = 0.642, P<0.001), tumor stage (r = 0.546, P<0.001), node stage (r = 0.388, P<0.001), and overall stage (r = 0.445, P= 0.000). Conclusion: Higher primary tumor SUVmax predicts higher extensional or metastatic potential in patients with NSCLC. Patients with higher SUVmax may need a close follow-up and more reasonable individual treatment because of their higher extensional and metastatic potential.
Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be targeted for refolding or degradation to maintain the homeostasis of the ER. Derlin-1 was reportedly implicated in the retro-translocation of misfolded proteins from the ER to the cytosol for degradation. In this report, we showed that Derlin-1 was down-regulated in the endothelial cells derived from human hepatic cavernous hemangioma (CHEC) compared with other tested cells. Electron microscopy analysis showed that ER was aberrantly enlarged in CHEC cells, but not in other tested cells. When overexpressed, Derlin-1 induced the dilated ER to return normal size. This ER dynamic was associated with the activation of unfolded protein response (UPR). In CHEC cells where Derlin-1 was down-regulated, increased expression of the immunoglobulin heavy chain-binding protein (Bip) and UPR-specific splicing of X-box DNA-binding protein 1 (XBP1) mRNA were detected, as compared with that in other tested cells, indicating that UPR was activated. After Derlin-1 overexpression, the extent of UPR activation diminished, as evidenced by decreased expression of Bip, reduced amount of the spliced form of XBP1 ($XBP1_S$), and elevated expression of the unspliced form of XBP1 ($XBP1_U$). Taken together, these findings provide another example of a single protein being able to affect ER dynamic in mammalian cells, and an insight into the possible molecular mechanism(s).
한국정보디스플레이학회 2009년도 9th International Meeting on Information Display
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pp.421-427
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2009
We successfully fabricated 4.7-inch organic thin film transistors array with $640{\times}480$ pixels on flexible substrate. All the processes were done by photolithography, spin coating and ink-jet printing. The OTFT-Electrophoretic (EP) pixel structure, based on a top gate OTFT, was fabricated. The mobility, ON/OFF ratio, subthreshold swing and threshold voltage of OTFT on flexible substrate are: 0.01 ^2/V-s, 1.3 V/dec, 10E5 and -3.5 V. After laminated the EP media on OTFT array, a panel of 4.7-inch $640{\times}480$ OTFT-EPD was fabricated. All of process temperature in OTFT-EPD is lower than $150^{\circ}C$. The pixel size in our panel is $150{\mu}m{\times}150{\mu}m$, and the aperture ratio is 50 %. The OTFT channel length and width is 20 um and 200um, respectively. We also used OTFT to drive EP media successfully. The operation voltages that are used on the gate bias are -30 V during the row data selection and the gate bias are 0 V during the row data hold time. The data voltages that are used on the source bias are -20 V, 0 V, and 20 V during display media operation.
The chigger mite Leptotrombidium sialkotense is one of the 6 main vectors of scrub typhus in China. Before present study, L. sialkotense was found in some parts of Hunan province, China with a narrow geographical distribution. During field investigation 2016-2017, we found L. sialkotense in Jingha, southern Yunnan, China. Of 15 small mammal host species, L. sialkotense were collected from 6 species of the hosts. Rattus brunneusculus was a dominant host of L. sialkotense, from which 98.3% of the mites were collected. The chigger mite showed a relatively high infestation prevalence (PM =11.7%) and mean abundance (MA=0.5) in comparison with the rest 5 host species. These results reveal a certain host specificity of L. sialkotense to a rat R. brunneusculus. The mite L. sialkotense showed an aggregated distribution on the host (P<0.05). A positive correlation observed between L. sialkotense and the body length of hosts. There was a positive interspecific association between L. sialkotense and 2 other dominant vectors, L. deliense and L. scutellare.
Yu, Qin Ping;Feng, Ding Yuan;He, Xiao Jun;Wu, Fan;Xia, Min Hao;Dong, Tao;Liu, Yi Hua;Tan, Hui Ze;Zou, Shi Geng;Zheng, Tao;Ou, Xian Hua;Zuo, Jian Jun
Asian-Australasian Journal of Animal Sciences
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제30권11호
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pp.1620-1632
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2017
Objective: This study evaluated the effects of a traditional Chinese medicine formula (TCMF) on muscle fiber characteristics in finishing pigs and the effects of the formula's extract (distilled water, ethyl acetate and petroleum ether extraction) on porcine cell proliferation and isoforms of myosin heavy chain (MyHC) gene expression in myocytes. Methods: In a completely randomized design, ninety pigs were assigned to three diets with five replications per treatment and six pigs per pen. The diets included the basal diet (control group), TCMF1 (basal diet+2.5 g/kg TCMF) and TCMF2 (basal diet+5 g/kg TCMF). The psoas major muscle was obtained from pigs at the end of the experiment. Muscle fiber characteristics in the psoas major muscle were analyzed using myosin ATPase staining. Cell proliferation was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye and cytometry. Isoforms of MyHC gene expression were detected by real-time quantitative polymerase chain reaction. Results: The final body weight and carcass weight of finishing pigs were increased by TCMF1 (p<0.05), while the psoas major muscle cross-sectional area was increased by TCMF (p<0.05). The cross-sectional area and diameter of psoas major muscle fiber Ι, IIA, and IIB were increased by TCMF2 (p<0.05). The cross-sectional area and fiber diameter of psoas major muscle fiber IIA and IIB were increased by diet supplementation with TCMF1 (p<0.05). Psoas major muscle fiber IIA and IIB fiber density from the pigs fed the TCMF1 diet and the type IIB fiber density from the pigs fed the TCMF2 diet were lower compared to pigs fed the control diet (p<0.05). Pigs fed TCMF2 had a higher composition of type Ι fiber and a lower percentage of type IIB fiber in the psoas major muscle (p<0.05). The expression levels of MyHC Ι, MyHC IIa, and MyHC IIx mRNA increased and the amount of MyHC IIb mRNA decreased in the psoas major muscle from TCMF2, whereas MyHC Ι and MyHC IIx mRNA increased in the psoas major muscle from TCMF1 (p<0.05). Peroxisome proliferator-activated receptor ${\gamma}$$coactivator-1{\alpha}$ and CaN mRNA expression in the psoas major muscle were up-regulated by TCMF (p<0.05). Porcine skeletal muscle satellite cell proliferation was promoted by $4{\mu}g/mL$ and $20{\mu}g/mL$ TCMF water extraction (p<0.05). Both $1{\mu}g/mL$ and $5{\mu}g/mL$ of TCMF water extraction increased MyHC IIa, MyHC IIb, and MyHC IIx mRNA expression in porcine myocytes (p<0.05), while MyHC Ι mRNA expression in porcine myocytes was decreased by $5{\mu}g/mL$ TCMF water extraction (p<0.05). Porcine myocyte MyHC Ι and MyHC IIx mRNA expression were increased, and MyHC IIa and MyHC IIb mRNA expression were down-regulated by $5{\mu}g/mL$ TCMF ethyl acetate extraction (p<0.05). MyHC Ι and MyHC IIa mRNA expression in porcine myocytes were increased, and the MyHC IIb mRNA expression was decreased by $1{\mu}g/mL$ TCMF ethyl acetate extraction (p<0.05). Four isoforms of MyHC mRNA expression in porcine myocytes were reduced by $5{\mu}g/mL$ TCMF petroleum ether extraction (p<0.05). MyHC IIa mRNA expression in porcine myocytes increased and MyHC IIb mRNA expression decreased by $1{\mu}g/mL$ in a TCMF petroleum ether extraction (p<0.05). Conclusion: These results indicated that TCMF amplified the psoas major muscle cross-sectional area through changing muscle fiber characteristics in finishing pigs. This effect was confirmed as TCMF extraction promoted porcine cell proliferation and affected isoforms of MyHC gene expression in myocytes.
The present study was conducted to evaluate radioimmunoimaging (RII) and in vivo distribution of mixed antibodies $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb in nude mice bearing human lung adenocarcinoma xenografts. Single and mixed applications of the two radiolabeled monoclonal antibodies (mAbs) were compared. Direct labeling of $^{99m}Tc$ was applied to radiolabel the EGFR and CD44 mAbs. The properties of the radiolabeled antibodies were then characterized. RII and assessment of the distribution of the antibodies in nude mice bearing lung adenocarcinoma xenografts were achieved by applying separate and combined doses of $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb. The labeling rates of $^{99m}Tc$ for EGFR-mAb and CD44-mAb were $91.5%{\pm}3.8%$ and $92.3%{\pm}4.1%$ respectively, with specific activities of 2.8 and $2.9MBq/{\mu}g$, respectively, and radiochemical purities (RCP) of 96.5% and 96.2%. The radioactivity uptake of the combined application of both radiolabeled antibodies was clearly higher than with a single application of either alone. The relative values of target-to-nontarget (T/NT) measured through the regional interest (ROI) technique were $5.59{\pm}0.42$ (mixed antibodies), $2.78{\pm}0.20$ ($^{99m}Tc$-EGFR-mAb), and $2.28{\pm}0.16$ ($^{99m}Tc$-CD44-mAb) in the RII. The body distribution of the radiolabeled antibodies and their imaging results were basically identical. Application of the mixed antibodies with $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb can increase the radioactivity uptake of tumor tissue, leading to more ideal target-to-nontarget ratios, and therefore superior results.
Gastric cancer continues to be a leading cause of cancer death. The majority of patients with gastric adenocarcinoma in China present with advanced disease. Ruling out unresectable cancers from an unnecessary "open" exploration is very important. The aim of this study was to assess the value of five-port anatomical laparoscopic exploration in T4 gastric cancer in comparison with three-port laparoscopic exploration and laparotomy exploration. We conducted a retrospective study on 126 patients with T4 stage scheduled for D2 curative gastrectomy based on computed tomography (CT) staging at Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, from Apr. 2011 to Apr. 2013. Laparotomy exploration (Group I), three-port laparoscopic exploration (Group II) or five-port anatomical laparoscopic exploration (Group III) were performed prior to radical gastrectomy. Accuracy rate for feasibility of D2 curative gastrectomy in laparotomy exploration and five-port anatomical laparoscopic exploration groups was higher than that in the three-port laparoscopic exploration group. Five-port anatomical laparoscopic exploration group had the highest accuracy resection rate (Group I vs Group II vs Group III,92.6% vs78.6% vs 97.7%; p<0.05) and shorter length of hospitalization (Group I vs Group II vs Group III, $9.58{\pm}4.17$ vs $6.13{\pm}2.85$ vs $5.00{\pm}1.81$; p<0.001). Three-port laparoscopic exploration has low accuracy rate for assessing feasibility of D2 curative gastrectomy and five-port anatomical laparoscopic exploration should be performed on patients with T4 gastric cancer.
The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.
Purpose: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. Patients and Methods: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. Results: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR: 38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. Conclusion: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.
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