scholarly journals The Essential Role of Nuclear β-Catenin Translocation in the Osteoblastic Differentiation of GCTB: Prediction of Tumor Ossification After Denosumab Treatment

Author(s):  
Atsushi Kimura ◽  
Yu Toda ◽  
Yoshihiro Matsumoto ◽  
Hidetaka Yamamoto ◽  
Kenichiro Yahiro ◽  
...  

Abstract Denosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker regarding tumor ossification of GCTB has not been elucidated. In this study, we investigated the relationship between Wnt/β-catenin signaling and the ossification of GCTB and evaluated whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. Genuine patient-derived primary GCTB tumor stromal cells exhibited osteoblastic characteristics. Identified osteoblastic markers and nuclear β-catenin translocation were significantly upregulated via differentiation induction and were inhibited by treating with Wnt signaling inhibitor, GGTI-286, or selective Rac1-LEF inhibitor, NSC23766. Furthermore, we reviewed the endogenous ossification and nuclear β-catenin translocation of 86 GCTB clinical samples and elucidated that intra-tumoral ossification was significantly associated with the nuclear translocation. Three-dimensional quantitative analyses (n = 13) of tumoral CT images have revealed that the nuclear β-catenin translocation of naïve GCTB samples was significantly involved with the denosumab-induced tumor ossification. Our findings suggest a close relationship between the nuclear β-catenin translocation and the osteoblastic differentiation of GCTB. Investigations of the nuclear β-catenin in naïve GCTB samples may provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.

2021 ◽  
Author(s):  
Atsushi Kimura ◽  
Yu Toda ◽  
Yoshihiro Matsumoto ◽  
Hidetaka Yamamoto ◽  
Kenichiro Yahiro ◽  
...  

Abstract BackgroundDenosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker in terms of post-administration ossification of the tumors has not been elucidated. The aims of this study were to investigate the relationship between Wnt/β-catenin signaling and the ossification of GCTB and to evaluate whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. MethodsWe established cultures of patient-derived primary GCTB stromal cells (pGCTB-SCs) and assessed the osteoblastic characteristics of pGCTB-SCs using cytochemical staining, optical density method (405 nm), and immunocytochemistry. Several mRNA expressions of osteoblastic markers (ALP, collagen type Ⅰ alpha 1 (COL1A1), integrin-binding sialoprotein (IBSP), runt-related transcription factor2 (RUNX2), and bone gamma-carboxyglutamate protein (BGLAP) was also investigated using quantitative real-time PCR (qRT-PCR) analysis. The impact on nuclear β-catenin translocation (NBT) by differentiation-induction was evaluated using Western blotting and immunocytochemistry. Wnt signaling inhibitor, GGTI-286, and selective Rac1 inhibitor, NSC23766, were added with OGM to evaluate the essential role of NBT. Furthermore, the distribution of endogenous NBT and the relationship with the tumoral ossification were assessed. Its predictability for the ossification in GCTB was also evaluated using a nuclear β-catenin labeling index (NBLI) of clinical samples (n = 86) and quantitative analyses of CT images.ResultspGCTB-SCs significantly expressed the osteoblastic markers with osteogenic medium (OGM) in a time-dependent manner (P < 0.0001, vs. vehicle). NBT was upregulated within 12 hours after OGM treatment. In addition, decreasing NBT by treatment with 40μM GGTI-286 significantly abolished the osteoblastic differentiation of pGCTB-SCs (P < 0.0001, vs. OGM). The selective Rac1 inhibitor, NSC23766, also suppressed the OGM-induced osteoblastic differentiation and NBT in pGCTB-SCs. Furthermore, in GCTB clinical samples, the NBTs were significantly associated with the tumor ossification following denosumab treatment (P = 0.003 for entire and peripheral tumor, and P = 0.02 for intra-tumor of GCTB) as well as endogenous intra-tumoral ossification. ConclusionsIn summary, our findings suggest a close relationship between the NBT and the osteoblastic differentiation of GCTB. Investigations of NBTs in naïve GCTB samples will provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.


Author(s):  
NIKE WIDURI ◽  
MIDIANSYAH EFFENDI ◽  
HERSON HERSON

This study aimed to know the role of agricultural extension in the development of tomato cultivation, the application level of tomato cultivation technology, and the relationship between the role of agricultural extension.  The sampling method in this study was stratified random sampling. The data were analyzed by using Rank Spearman. The results showed that the role of agricultural extension in the technology of tomato cultivation was very important position with an average score of 39.16, the level of application of tomato cultivation technology was in a high position with an average score of 45.47, there is a close relationship between the role of agricultural extension with the application level of tomato cultivation technology.


2001 ◽  
Author(s):  
K. B. Chandran ◽  
S. D. Ramaswamy ◽  
Y.-G. Lai ◽  
A. Wahle ◽  
M. Sonka

Abstract Complete occlusion in any of the coronary vessels leads to a myocardial infarction. The role of fluid mechanical forces in atheroma development has been widely accepted because of preferential plaque growth at certain locations of the vessel geometry, such as a bifurcation or regions of high degrees of curvature. Areas of low and/or oscillatory shear stress have been correlated with atheroma development [1]. In order to determine the relationship between fluid mechanical stresses and development of lesions in the coronary vessels, it is important to analyze the fluid mechanics in actual three-dimensional geometries, incorporating the time-dependent translation and geometric alterations of these vessels [2,3].


2002 ◽  
Vol 30 (5) ◽  
pp. 515-525 ◽  
Author(s):  
Rumi Matsushima ◽  
Kunio Shiomi

Close relationship during adolescence plays an important role in the young person's overall psychological development. As the most important factor about the development of a close relationship, many studies have emphasized the role of self-disclosure. In this study, the relationship between self-disclosure and friendship in adolescence was examined.Two scales about self-disclosure and friendship were administered to 454 junior high school students. The types of friendship in early adolescence were explored, and the relationship between types of friendship and self-disclosure was examined.


2021 ◽  
Vol 13 (11) ◽  
pp. 6140
Author(s):  
Marica Barbaritano ◽  
Elisabetta Savelli

Consumer environmental responsibility has been commonly considered as an antecedent to green consumption intention and eco-design purchases. However, little research has investigated how environmental concern affects the relationship between design attributes and purchasing intention, especially in the furniture setting, where companies are often involved in design-intensive processes and environmental problems. This study investigates (i) how consumers perceive the different dimensions of design and which attributes most affect their purchasing intention of furniture items; and (ii) the role of consumers’ environmental responsibility on the relationship between design attributes and purchasing intention. An online questionnaire survey was employed to collect data from 350 Italian consumers. The findings reveal that design can be intended as a three-dimensional construct, based on functional, aesthetic, and symbolic attributes. While functional and aesthetic features can be considered as relevant factors affecting the consumers’ perception of design, the purchasing intention is mainly influenced by the symbolic dimension of design. Moreover, environmental concern moderates the relationship between the symbolic dimension of design and purchasing intention, that is, when consumers are highly concerned about environmental issues, they tend to be more influenced by the symbolic dimension of design. Several theoretical and practical implications are discussed.


Jurnal Ecopsy ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Maya Irka Anggriani ◽  
Hemy Heryati Anward ◽  
Rooswita Santia Dewi

Penelitian ini bertujuan untuk mengetahui ada tidaknya peranan suasana kerja terhadap keinginan pindah kerja karyawan. Populasi pada penelitian ini yaitu seluruh karyawan PT. Hasnur Jaya Utama. Jenis pengambilan sampel yang dilakukan pada penelitian ini adalah Purposive Random Sampling yaitu pemilihan sampel secara acak sesuai dengan karakteristik yang ditentukan berdasarkan tujuan penelitian yang berjumlah 60 orang.  Sedangkan metode pengumpulan data dengan menggunakan skala suasana kerja, skala kepuasan kerja dan kuesioner keinginan pindah kerja. Dalam penelitian ini analisis data menggunakan analisis regresi linear sederhana. Hasil analisis peranan suasana kerja terhadap kepuasan kerja, diperoleh koefisien korelasi R sebesar 0,759 artinya hubungan suasana kerja dan kepuasan kerja erat. Ditemukan juga koefisien determinasi (R2) yang menunjukkan peranan suasana kerja terhadap kepuasan kerja sebesar 57,5% dan untuk analisis t observasi (8,882) > t tabel (1,672) menunjukkan  ada peranan suasana kerja terhadap kepuasan kerja. Kemudian, hasil analisis peranan kepuasan kerja terhadap keinginan pindah kerja ditemukan koefisien regresi R (0,680) artinya kepuasan kerja dan keinginan pindah kerja memiliki hubungan yang cukup erat. Selanjutnya, diperoleh juga (R2) yang menunjukkan peranan kepuasan kerja terhadap keinginan pindah kerja sebesar 46,3%  dan   untuk  analisis   t   observasi (-7,069) t tabel (1,672) menunjukkan ada peranan kepuasan kerja terhadap keinginan pindah kerja dengan signifikan negatif. Berdasarkan hasil penelitian tersebut maka dapat ditarik kesimpulan bahwa suasana kerja dan kepuasan kerja pada karyawan perlu diperhatikan oleh perusahaan agar dapat meminimalkan keinginan pindah kerja karyawan. Kata Kunci: Suasana kerja, kepuasan kerja, keinginan pindah kerjaThis study purposed to determine whether there is the influence of the working atmosphere to intention turnover on employees. The population in this study are all employees of PT. Hasnur Jaya Utama. Type of sampling conducted in this study is Purposive Random Sampling is the selection of a random sample according to the characteristics that are determined based on the research goals of 60 people. The methods of data collection by using the scale of the working atmosphere, the scale of job satisfaction and intention turnover questionnaire. In this study analyzes the data using simple linear regression analysis. The results of the analysis of the influence of working atmosphere to job satisfaction, the correlation coefficient R of 0.759 means that the relationship working atmosphere and job satisfaction is quite close. Also found the coefficient of determination (R2) which indicates the role of working conditions on job satisfaction at 57.5% and for the analysis of observation (8.882) > t table (1.672) which indicates means that the influence of the atmosphere to job satisfaction. Then, the results of the analysis of the influence of job satisfaction to intention turnover a correlation coefficient R (0.680) means that job satisfaction and intention turnover to have a close relationship. Furthermore, also obtained (R2 ) which indicates the role of job satisfaction to intention turnover of 46,3% and for the analysis of t observation (-7.069) > t table (1.672) which indicates means that the influence of job satisfaction to intention turnover with a significant negative . Based on these results it can be concluded that the working atmosphere and job satisfaction in employees need to be considered by the company in order to minimize intention turnover ob the employees. Keywords: The working atmosphere, job satisfaction, intention turnover.


Author(s):  
ERICA FATMITA RAMADANI ◽  
DINA LESMANA ◽  
MIDIANSYAH EFFENDI

The purposes of this research were to know the role of Field Agriculture Instructor (FAI) in the development of Farmers Groups Association (FGA), the development of FGA, and the relationship between the role of FAI and the development of FGA. This research was conducted during three months from August to October 2015. The role of FAI in the development of FGA was analyzed by using Chi Square. The relationship between the role of FAI and the development of FGA was test by using Rank Spearman.   The results of this research show that the role of FAI shows with the score of 39.27 and the development of FGA with the score of 36.79. The results of data analysis show χ2count of 8.06 and χ2table (α = 0.05) of 3.84 also tcount of  3.92 and ttable (α = 0,05) of 1.68 so that can be concluded that there is a close relationship between the role of FAI and the development of FGA in Wonosari Village, Sepaku Subdistrict, Penajam Paser Utara District.


Author(s):  
John H. Harvey ◽  
Brian G. Pauwels

Achieving constructive relationship connections is an important step as an objective of positive psychology. In the context of a culture of dissolution in close relationships, minding serves as an antidote to the demise of feelings of closeness overtime. In this paper, we argue that minding the close relationship is a powerful pathway to developing and enhancing closeness. Minding is a combination of thought and behavior patterns that interact to create stability and feelings of closeness. Minding is formally defined as a reciprocal knowing process that occurs nonstop throughout the history of the relationship and that involves a complex package of interrelated thoughts, feelings, and behaviors. The components of minding are knowing and being known, achieved through reciprocal self-disclosure; attribution that is realistic about causality, but that also gives one's partner the benefit of doubt in questionable circumstances; acceptance of what one discovers in the knowing process and respect for one's partner revealed in this process; and reciprocity and continuity. The final component emphasizes the fact that minding must be done by both partners and that it is a never-ending process. The paper also describes other contemporary conceptions to which minding is closely related and addresses future direction for research on the minding process.


2019 ◽  
Vol 9 (6) ◽  
pp. 128 ◽  
Author(s):  
Paul E. Engelhardt ◽  
Gavin Nobes ◽  
Sophie Pischedda

The relationship between ADHD—in particular hyperactivity—and criminal behavior is well documented. The current study investigated the role of criminogenic cognitions in the explanation of this relationship by examining which symptoms of ADHD are associated with criminogenic cognitions. Community-recruited adults (N = 192) completed self-report questionnaires for symptoms of ADHD and criminogenic cognitions. Symptoms of inattention were consistently and strongly related to criminogenic cognitions. In particular, inattention was significantly related to cutoff, cognitive indolence, and discontinuity. There was also evidence that impulsivity was positively related to criminogenic cognitions, and specifically, to the power orientation subscale. In contrast, and contrary to expectations, symptoms of hyperactivity were not related to criminogenic cognitions. These results indicate that in community-recruited adults, inattention rather than hyperactivity is related to criminogenic cognitions. We discuss the implications of these findings contrasting with those of previous studies that used forensic and clinical samples.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xia Liao ◽  
Yang Bu ◽  
Fan Chang ◽  
Fengan Jia ◽  
Ge Song ◽  
...  

Abstract Background Hepatic stellate cells (HSCs) have a key role in fibrogenesis and in the filtrates of the hepatocellular carcinoma (HCC) stroma, in which they are remodeled and play a critical role in HCC progression. However, the precise role of HSCs trending, infiltration and paracrine in orchestrating the stroma-derived oxaliplatin-resistance in HCC is still vague. Methods The chemo-resistant models were established to explore the correlation between HSC cells and the condition of chemoresistance. The HCC clinical samples were collected to confirm this phenomenon. Then, the relationship between secretory CCN3 from oxaliplatin-resistant HCC and the infiltration of HSCs in associated HCC microenvironment was evaluated. Finally, the role and mechanism of HSCs remodeling in the orchestration of oxaliplatin-resistant HCC were explored. Results The increased infiltration of HSCs and collagen accumulation were found in the microenvironment of oxaliplatin-resistant HCC. The cDNA profiles of the oxaliplatin-resistant HCC was reanalyzed, and CCN3 was one of the significantly increased genes. In HCC clinical samples, the levels of CCN3 and α-SMA are positively correlated, and high expression of CCN3 and α-SMA are positively associated with malignant phenotype and poor prognosis. Then the enhanced abilities of migration and proliferation of HSCs, and elevation of the cytokines paracrine from HSCs relating to HCC malignancy were proved in vitro and in vivo, and which were related to CCN3-ERK signaling pathway activation. Conclusions HSCs remodeling are positively related to CCN3 paracrine in hepatocellular carcinoma, which orchestrated the stroma-derived resistance to chemotherapy in HCC.


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