POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and ...biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.
Frequency of FGFR2 amplification, its clinicopathological features, and the results of high-throughput screening assays in a large cohort of gastric clinical samples remain largely unclear.
Drug ...sensitivity to a fibroblast growth factor receptor (FGFR) inhibitor was evaluated in vitro. The gene amplification of the FGFRs in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues was determined by a real-time PCR-based copy number assay and fluorescence in situ hybridisation (FISH).
FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. The copy number assay revealed that 4.1% (11 out of 267) of the gastric cancers harboured FGFR2 amplification. No amplification of the three other family members (FGFR1, 3 and 4) was detected. A FISH analysis was performed on 7 cases among 11 FGFR2-amplified cases and showed that 6 of these 7 cases were highly amplified, while the remaining 1 had a relatively low grade of amplification. Although the difference was not significant, patients with FGFR2 amplification tended to exhibit a shorter overall survival period.
FGFR2 amplification was observed in 4.1% of gastric cancers and our established PCR-based copy number assay could be a powerful tool for detecting FGFR2 amplification using FFPE samples. Our results strongly encourage the development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification.
This study aimed to test the role of family social support, depression, anxiety and self-efficacy on specific self-care behaviours. In a local community health center, 318 patients with hypertension ...completed a questionnaire assessing self-care, family social support, depression, anxiety and self-efficacy in 2012. Each self-care behaviour was separately analyzed with logistic regression models. The mean score of perceived family social support for hypertension treatment was 20.91 (maximum=60). Adult children were identified as the primary support source. Approximately 22.3% and 15.4% of participants reported symptoms of anxiety and depression, respectively. Participants had moderately positive levels of confidence performing self-care (42.1±13.3 out of 60). After adjusting for demographic and health variables, a 10-unit increase in family social support increased the odds ratio (OR) of taking medication by 1.39 (95% confidence interval (CI) 1.03-1.87) and increased the OR for measuring blood pressure (BP) regularly by 1.33 (95% CI 1.02-1.74). Depression and anxiety were not associated with any self-care behaviours. A10-unit increase in self-efficacy increased the adjusted OR for performing physical exercise to 1.25 (95% CI 1.04-1.49). In conclusion, family social support was positively associated with medication adherence and regular BP measurement. Strategies to improve family social support should be developed for hypertension control, yet further prospective studies are needed to understand the effects of family social support, depression, anxiety and self-efficacy on self-care behaviours.
Genotypic variations in cadmium levels of rice grain Arao, T. (National Inst. for Agro-Environmental Sciences, Tsukuba, Ibaraki (Japan)); Ae, N
Soil science and plant nutrition (Tokyo),
08/2003, Letnik:
49, Številka:
4
Journal Article
Recenzirano
Odprti dostop
To identify rice grain genotypes with a lower cadmium content,49 cultivars of rice were tested under upland conditions, using two types of soils contaminated with cadmium (A: alluvial and B: volcanic ...ash soil) in 1999 and 2000. Results of ranking of grain cadmium concentrations were similar between these 2 years. NIPPONBARE,KOSHIHIKARI,and HU-LO-TAO belonged to the rice grain group with the lowest cadmium contents. KASALATH could be categorized as a variety with a medium cadmium content, hereafter referred to as "medium cadmium variety," and MILYANG23 and PEH-KUH-TSAO-TU as varieties with high cadmium contents, hereafter referred to as "high cadmium varieties." These five varieties except for HU-LO-TAO from the above six typical varieties were grown in submerged pots (paddy conditions), and the ranking of the grain cadmium content was almost the same as that in the upland condition pots. These results imply that it may be possible to select paddy rice varieties with a low cadmium content even when growth occurred under upland conditions. The possibility of screening for lower cadmium content in rice grain in solution culture was examined. The shoot cadmium concentrations in solution culture were not significantly lower in NIPPONBARE and KOSHIHIKARI than those of MILYANG23 and PEH-KUH-TSAO-TU after 4 d of cadmium addition. Only PEH-KUH-TSAO-TU showed a higher shoot cadmium concentration than the other varieties after 27 d of cadmium addition. Thus, as a preliminary evaluation, a screening method using solution culture would not be suitable for detecting genotypes with a low cadmium content in grain within 1 month after cadmium addition. Our results suggest that the status of available cadmium in soil differs from that of available cadmium in solution culture. Cadmium distribution for grain (i.e., grain cadmium content ratio to total uptake in the terrestrial part of plants) was evaluated among these 5 varieties. KASALATH absorbed a relatively high amount of cadmium, although cadmium distribution to grain in KASALATH was the lowest among the 5 varieties. On the other hand, in MILYANG23, a much higher amount of cadmium was translocated to the grain than in the other 4 varieties, suggesting the existence of genetic variability in cadmium translocation from shoots to grains.
The mechanisms underlying cellular drug resistance have been extensively studied, but little is known about its regulation. We have previously reported that activating transcription factor 4 (ATF4) ...is upregulated in cisplatin-resistant cells and plays a role in cisplatin resistance. Here, we find out a novel relationship between the circadian transcription factor Clock and drug resistance. Clock drives the periodical expression of many genes that regulate hormone release, cell division, sleep-awake cycle and tumor growth. We demonstrate that ATF4 is a direct target of Clock, and that Clock is overexpressed in cisplatin-resistant cells. Furthermore, Clock expression significantly correlates with cisplatin sensitivity, and that the downregulation of either Clock or ATF4 confers sensitivity of A549 cells to cisplatin and etoposide. Notably, ATF4-overexpressing cells show multidrug resistance and marked elevation of intracellular glutathione. The microarray study reveals that genes for glutathione metabolism are generally downregulated by the knockdown of ATF4 expression. These results suggest that the Clock and ATF4 transcription system might play an important role in multidrug resistance through glutathione-dependent redox system, and also indicate that physiological potentials of Clock-controlled redox system might be important to better understand the oxidative stress-associated disorders including cancer and systemic chronotherapy.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in response to growth factors and cytokines, and which contributes to the regulation of cell ...proliferation, apoptosis, and motility in many human tumour types.
We investigated the mechanisms of STAT3 activation and the function of STAT3 depending on its mechanism of activation in gastric cancer cells.
The MET-tyrosine kinase inhibitor (TKI) and cell transfection with a small interfering RNA (siRNA) specific for MET mRNA inhibited STAT3 phosphorylation in MET-activated cells, indicating that STAT3 activation is linked to MET signalling. Forced expression of a constitutively active form of STAT3 also attenuated MET-TKI-induced apoptosis, suggesting that inhibition of STAT3 activity contributes to MET-TKI-induced apoptosis. MKN1 and MKN7 cells, both of which are negative for MET activation, produced interleukin-6 (IL-6) that activated STAT3 through the Janus kinase pathway. Depletion of STAT3 by siRNA inhibited migration and invasion of these cells, suggesting that STAT3 activated by IL-6 contributes to regulation of cell motility.
Our data thus show that activated STAT3 contributes to either cell survival or motility in gastric cancer cells, and that these actions are related to different mechanisms of STAT3 activation.
Objective
The aim of this study was to evaluate the association of IL17A G197A polymorphism and serum levels with oral lichen planus (OLP) susceptibility and clinical presentation.
Subjects and ...Methods
Eighty‐three individuals diagnosed with OLP and 99 healthy controls (C) were consecutively recruited. All participants had desquamating oral mucosal cells collected and DNA isolated for IL17A (G197A) genotyping. Blood samples of 42 OLP individuals and 23 healthy controls were collected for evaluation of IL17A serum levels.
Results
IL17A G197A genotypes were associated with an increased chance of having OLP (GA/AA × GG, OR = 3.44, 95% CI = 1.87–6.33, p < .001). Overall A carriers (GA or AA) were more common in OLP (38.1%) than in C (20.2%; OR = 2.43, 95% CI = 1.53–3.87, p < .001). Serum levels of IL17A were higher among patients with OLP than in healthy controls (reticular, p = .0003; erosive, p < .001), but no difference was found among the disease types.
Conclusions
IL17A G197A is associated with a higher susceptibility of developing OLP and these patients seem to present a considerable increase in IL17A serum levels. These findings suggest that Th17 cells, and IL17A in particular, may play a pivotal role in OLP pathogenesis.
Activin A is a multi-functional cytokine belonging to the transforming growth factor-β (TGF-β) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that ...inhibin β A subunit (INHBA) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC.
Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs) in vitro and a stable INHBA-introduced GC cell line in vivo.
Compared with TGF-β, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable INHBA-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis in vivo.
Our findings highlight the suppressive role of activin A, unlike TGF-β, on tumour growth and angiogenesis in GC.
Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated ...with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of high-grade gliomas in a more objective manner than standard pathology. RNAs from 29 malignant gliomas were analysed using Agilent microarrays. We identified 21 genes whose expression was most strongly and consistently related to patient survival based on univariate proportional hazards models. In six out of 10 genes, changes in gene expression were validated by quantitative real-time PCR. After adjusting for clinical covariates based on a multivariate analysis, we finally obtained a statistical significance level for DDR1 (discoidin domain receptor family, member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was confirmed that DDR1 protein expression was also correlated to the prognosis of glioma patients detected by immunohistochemical staining. Furthermore, we analysed the efficacy of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA synthesis in glioma cell lines. Cell proliferation and invasion were significantly suppressed by siRNA against DDR1. Thus, DDR1 can be a novel molecular target of therapy as well as an important predictive marker for survival in patients with glioma. Our method was effective at classifying high-grade gliomas objectively, and provided a more accurate predictor of prognosis than histological grading.
In order to investigate the genetic differences in uptake and distribution of cadmium in soybeans, 17 varieties of soybean were grown first in soil and then four or five varieties of soybean were ...grown in nutrient solution with different levels of cadmium.Significant genotypic differences in seed cadmium levels were found. The seed cadmium concentration was lowest for the En-b0-1-2 soybean variety, and highest for Harosoy, in both field and pot experiments. The seed cadmium levels of Tohoku 128, a cross between Enrei and Suzuyutaka, were intermediate between those of the parents. For four soil types, containing from 0.2 to 6.5 mg kg-1 extractable cadmium, the ranking of soybean genotypes based on seed cadmium level was similar, indicating that there is a genetic factor involved in the varietal differences in cadmium concentration. Among the four soybean varieties tested in one experiment in the present study, the cadmium concentrations in leaves, stems and pods as well as the total cadmium uptake were lowest for En-b0-1-2. These results suggest that cadmium uptake and/or translocation from root to shoot are low in En-b0-1-2. In solution culture containing 100 μg L-1 cadmium, the cadmium concentrations in seeds, stems and pods at the seed maturation stage were also the lowest for En-b0-1-2. In a second experiment, the cadmium concentrations in the leaves, stem and petiole were lower at both 7 and 15 days after the addition of cadmium to the nutrient solution for En-b0-1-2 and Enrei than for Tohoku 128, Suzuyutaka and Harosoy; however, the cadmium concentrations of roots for En-b0-1-2 and Enrei were higher than for the other varieties. We propose that the lower levels of cadmium found in the seeds of certain varieties of soybean result from the combination of lower initial uptake and retention of higher levels of cadmium in the roots, thus limiting its translocation to the shoot.
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