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Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.

Combination chemotherapy with gemcitabine and cisplatin (GC) is recommended as the primary treatment for advanced bladder cancer (BC). However, the benefits of this approach are limited owing to the acquisition of drug resistance. Here, we found that gemcitabine‐resistant and cisplatin‐resistant BCs do not exhibit cross‐resistance, and that these BCs exhibit different mRNA patterns, as revealed using RNA sequence analysis. To overcome drug resistance, we used the newly developed pan‐RAS inhibitor Compound 3144. Compound 3144 inhibited cell viability through suppression of RAS‐dependent signaling in gemcitabine‐ and cisplatin‐resistant BCs. RNA sequencing revealed that several genes and pathways, particularly those related to the cell cycle, were significantly downregulated in Compound 3144‐treated BCs. These findings provide insights into potential therapeutic strategies for treating BC.

Abstract Introduction The celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. At our affiliated institution, fluoroscopy-guided splanchnic nerve block with a single needle via the transintervertebral disc approach was the first choice of treatment. The short-term efficacy of this technique has been reported, but the long-term efficacy is not clear. In the present study, we investigated the long-term analgesic efficacy of this technique. Methods This multicenter, retrospective, observational study reviewed the medical records of patients who underwent neurolytic splanchnic nerve block (NSNB) via the transintervertebral disc approach for intractable cancer pain at five tertiary hospitals in Japan from April 2005 to October 2020. The primary outcome was the long-term analgesic efficacy of a one-time NSNB via the transintervertebral disc approach. Results In total, 76 patients were included in the analysis. The median lowest numerical rating scale (NRS) score was 1 within 14 days. At 1, 2, 3, and 6 months after the nerve block, the median NRS score was also ≤ 2, while the median equivalent oral morphine dose did not show any clinically noticeable increase at those times. Conclusion The long-term analgesic efficacy of NSNB via the transintervertebral disc approach in patients with intractable cancer pain has been demonstrated.

Introduction Metastasectomy of oligometastatic prostate cancer has the potential to contribute to improving prognosis. We report on a case of metastasectomy of solitary liver tumor after radical prostatectomy. Case presentation An 80‐year‐old man underwent radical prostatectomy for prostate cancer, followed by radiotherapy after the operation because of increased serum prostate‐specific antigen levels of 0.529 ng/mL. Levels increased further to 0.997 ng/mL even after salvage therapy. The patient then received androgen deprivation therapy. Levels remained stable for 3 years, but rapidly increased to 19.781 ng/mL in the following 6 months. Abdominal computed tomography revealed a solitary liver tumor, and no metastasis to other sites was identified. The patient underwent liver segmentectomy. Microscopic examination of excised specimens revealed prostate cancer cells. Five years after surgery, serum prostate‐specific antigen maintained to the lowest level so far. Conclusion Metastasectomy might be a beneficial therapeutic option to improve the prognosis for solitary metastasis from prostate cancer.

Abstract Background Complex anatomical features are challenging for minimally invasive intradiscal therapy owing to insufficient visualization for accurate needle advancement. We report the case of a patient with dysraphic vertebral pathologies who presented with L5/S1 degeneration and was successfully treated with annuloplasty using the cone-beam computed tomography (CBCT)-assisted radiofrequency thermocoagulation system. Case presentation A 34-year-old woman presented with a lower back and left radicular pain of L5/S1 discogenic origin, accompanied by spina bifida occulta and lumbosacral transitional vertebra. Radiofrequency annuloplasty was performed to preserve disc height and spinal stability, with real-time CBCT guidance for the congenital and degenerative conditions. The procedure relieved her left lower-extremity pain and magnetic resonance imaging revealed that the L5/S1 disc bulging decreased while the disc height was preserved. Conclusion Optimal accessibility of radiofrequency thermocoagulation and effective needle guidance using CBCT significantly improve the success rate of annuloplasty at the L5/S1 degenerative disc with severe vertebral deformity.

Background: Site-specific postoperative risk models for localized upper tract urothelial carcinoma (UTUC) are unavailable. Objective: To create specific risk models for renal pelvic urothelial carcinoma (RPUC) and ureteral urothelial carcinoma (UUC), and to compare the predictive accuracy with the overall UTUC risk model. Design, setting, and participants: A multi-institutional database retrospective study of 1917 UTUC patients who underwent radical nephroureterectomy (RNU) between 2000 and 2018 was conducted. Outcome measurements and statistical analysis: A multivariate hazard model was used to identify the prognostic factors for extraurinary tract recurrence (EUTR), cancer-specific death (CSD), and intravesical recurrence (IVR) after RNU. Patients were stratified into low-, intermediate-, high-, and highest-risk groups. External validation was performed to estimate a concordance index of the created risk models. We investigated whether our risk models could aid decision-making regarding adjuvant chemotherapy (AC) after RNU. Results and limitations: The UTUC risk models could stratify the risk of cumulative incidence of three endpoints. The RPUC- and UUC-specific risk models showed better stratification than the overall UTUC risk model for all the three endpoints, EUTR, CSD, and IVR (RPUC: concordance index, 0.719 vs 0.770, 0.714 vs 0.794, and 0.538 vs 0.569, respectively; UUC: 0.716 vs 0.767, 0.766 vs 0.809, and 0.553 vs 0.594, respectively). The UUC-specific risk model can identify the high- and highest-risk patients likely to benefit from AC after RNU. A major limitation was the potential selection bias owing to the retrospective nature of this study. Conclusions: We recommend using site-specific risk models instead of the overall UTUC risk model for better risk stratification and decision-making for AC after RNU. Patient summary: Upper tract urothelial carcinoma comprises renal pelvic and ureteral carcinomas. We recommend using site-specific risk models instead of the overall upper tract urothelial carcinoma risk model in risk prediction and decision-making for adjuvant therapy after radical surgery.

Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine‐resistant cells were established and resistance confirmed in vitro and in vivo. Small RNA sequencing analyses were performed to search for miRNAs involved in gemcitabine resistance. miR‐99a‐5p, selected as a candidate miRNA, was downregulated compared to its parental cells. In gain‐of‐function studies, miR‐99a‐5p inhibited cell viabilities and restored sensitivity to gemcitabine. RNA sequencing analysis was performed to find the target gene of miR‐99a‐5p. SMARCD1 was selected as a candidate gene. Dual‐luciferase reporter assays showed that miR‐99a‐5p directly regulated SMARCD1. Loss‐of‐function studies conducted with si‐RNAs revealed suppression of cell functions and restoration of gemcitabine sensitivity. miR‐99a‐5p overexpression and SMARCD1 knockdown also suppressed gemcitabine‐resistant cells in vivo. Furthermore, β‐galactosidase staining showed that miR‐99a‐5p induction and SMARCD1 suppression contributed to cellular senescence. In summary, tumor‐suppressive miR‐99a‐5p induced cellular senescence in gemcitabine‐resistant bladder cancer cells by targeting SMARCD1.

Purpose: Preoperative deep vein thrombosis (pre-DVT) is a risk of symptomatic venous thromboembolism (VTE) and a serious postoperative surgical complication. However, little is known about pre-DVT in patients undergoing surgery. This study aimed to investigate the incidence and screening criteria of pre-DVT in patients undergoing urological surgery. Materials and Methods: Between 2015 and 2017, 320 patients admitted to our hospital for urological surgery were included in this retrospective study. All patients underwent preoperative D-dimer testing. Patients with elevated D-dimer (≥1.0 µg/mL) levels underwent lower-limb compression ultrasonography (CUS). Clinical parameters were analyzed as predictors of pre-DVT, and modest cutoff value of D-dimer to predict pre-DVT were evaluated. Results: Of 320 patients, preoperative elevated D-dimer levels and DVT were found in 81 (25.3%) and 20 (6.3%) patients, respectively. The positive predictive value (PPV) was 24.7% (20/81). ROC curve analysis revealed a cutoff D-dimer level of 1.8 µg/mL, yielding a PPV of 40.7% for pre-DVT among patients with elevated D-dimer levels. Preoperative DVT was detected in 16 (7.6%, n=210) patients with malignancy, 3 (5.7%, n=53) with adrenal tumors, and in 1 (1.8%, n=57) kidney donor. An age of >70 years was significantly associated with risk for pre-DVT (odds ratio, 2.81; 95% confidence interval, 1.12–7.19; p=0.0270). During a postoperative follow-up period of 90 days, no patient developed symptomatic VTE. Conclusions: The incidence of pre-DVT was 6.3% in patients undergoing urological surgery. Elderly patients and/or a cutoff D-dimer level of 1.8 µg/mL might be good indications for pre-DVT screening by CUS.

Abstract Background Cisplatin-based chemotherapy is recommended as the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, the benefits are limited due to the acquisition of drug resistance. The mechanisms of resistance remain unclear. Although there are some reports that some molecules are associated with cisplatin resistance in advanced BC, those reports have not been fully investigated. Therefore, we undertook a new search for cisplatin resistance-related genes targeted by tumor suppressive microRNAs as well as genes that were downregulated in cisplatin-resistant BC cells and clinical BC tissues. Methods First, we established cisplatin-resistant BOY and T24 BC cell lines (CDDP-R-BOY, CDDP-R-T24). Then, Next Generation Sequence analysis was performed with parental and cisplatin-resistant cell lines to search for the microRNAs responsible for cisplatin resistance. We conducted gain-of-function analysis of microRNAs and their effects on cisplatin resistance, and we searched target genes comprehensively using Next Generation mRNA sequences. Results A total of 28 microRNAs were significantly downregulated in both CDDP-R-BOY and CDDP-R-T24. Among them, miR-486-5p, a tumor suppressor miRNA, was negatively correlated with the TNM classification of clinical BC samples in The Cancer Genome Atlas (TCGA) database. Transfection of miRNA-486-5p significantly inhibited cancer cell proliferation, migration, and invasion, and also improved the cells’ resistance to cisplatin. Among the genes targeted by miRNA-486-5p, we focused on enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (EHHADH), which is involved in the degradation of fatty acids. EHHADH was directly regulated by miRNA-486-5p as determined by a dual-luciferase reporter assay. Loss-of-function study using EHHADH si-RNA showed significant inhibitions of cell proliferation, migration, invasion and the recovery of cisplatin sensitivity. Conclusion Identification of EHHADH as a target of miRNA-486-5p provides novel insights into the potential mechanisms of cisplatin resistance in BC.

d‐3‐Phosphoglycerate dehydrogenase (PHGDH) conducts an important step in the synthesis of serine. Importantly, the PHGDH gene is often amplified in certain cancers. Our previous studies revealed that PHGDH gene amplification was associated with poor overall survival in clear cell renal cell carcinoma (ccRCC) and that metabolic reprogramming of serine synthesis through PHGDH recruitment allowed ccRCC cells to survive in unfavorable environments. There have been no investigations of the role of PHGDH expression in bladder cancer (BC). In this investigation, we examined the clinical importance of PHDGH in BC. Furthermore, we asked whether PHGDH expression could be exploited for BC therapy. Finally, we investigated the regulatory mechanisms that modulated the expression of PHGDH. Using data from The Cancer Genome Atlas, we found that patients with high‐grade BC had significantly higher PHGDH expression levels than did those with low‐grade BC. In addition, patients with high PHGDH expression did not survive as long as those with low expression. PHGDH downregulation by si‐RNAs or an inhibitor in BC cell lines significantly inhibited proliferative ability and induced apoptosis. Furthermore, combined treatment using a PHGDH inhibitor and gemcitabine/cisplatin achieved synergistic tumor suppression compared to use of a single agent both in vitro as well as in vivo. Mechanistic analyses of PHGDH regulation showed that PHGDH expression might be associated with DNA copy number and hypomethylation in BC. These findings suggest novel therapeutic strategies could be used in BC. Finally, our data enhance our understanding of the role of PHGDH in BC.

Abstract Background ABO-incompatible living related kidney transplantation (ABO-iLKT) has increased the possibilities for kidney transplantation in patients with end stage renal disease. Due to advancements in immunosuppressive agents and the identification of immunological conditions following ABO-iLKT, this transplantation technique has achieved the same success rate as ABO-compatible LKT. However, some patients continue to generate anti-blood type antibodies, despite conventional immunosuppressant treatment. Case presentation A 60-year-old man was referred to our hospital for kidney transplantation. The proposed transplant was ABO incompatible, from a donor with blood-type A to a recipient with blood-type O. The recipient’s anti-A blood-type IgG antibody titer was measured at 4096-fold dilution. Following desensitization therapy, including mycophenolate mofetil (MMF) 750 mg/day for 3 months, intravenous Rituximab 200 mg, and two sessions of double filtration plasmapheresis, the anti-A blood-type IgG antibody titer decreased to only 516-fold dilution and did not meet our target of less than 128-fold dilution. MMF was thus continued for an additional 4 months and four additional sessions of plasmapheresis were undertaken. Following these interventions, antibody titers decreased to 128-fold dilution and ABO-iLKT was performed. Following transplant, antibody-mediated rejection was not observed and renal function was preserved. However, a post-operative renal biopsy 1.5 months later showed evidence of T-cell-mediated rejection IB. The patient was treated with steroids, with no increase in serum creatinine. Conclusion Our findings suggest that the long-term single MMF desensitization therapy could be a suitable option for ABO-iLKT with high refractory and rebound anti-blood type antibody. Further studies are required to establish the optimal immunosuppression regimen to control B cell- mediated immunity in ABO-iLKT.

Exosomes are 40-100 nm nano-sized extracellular vesicles. They are released from many cell types and move into the extracellular space, thereby transferring their components to recipient cells. Exosomes are receiving increasing attention as novel structures participating in intracellular communication. RAB27B is one of the leading proteins involved in exosome secretion, and oncogenic effects have been reported in several cancers. In recent years, molecularly targeted agents typified by sunitinib are widely used for the treatment of metastatic or recurrent renal cell carcinoma (RCC). However, intrinsic or acquired resistance to sunitinib has become a major issue. The present study aimed to elucidate the role of RAB27B in RCC including sunitinib-resistant and its role in exosomes. Bioinformatic analyses revealed that high expression of RAB27B correlates with progression of RCC. The expression of RAB27B protein in RCC cell lines was significantly enhanced compared with that in normal kidney cell lines. Furthermore, RAB27B protein expression was enhanced in all of the tested sunitinib-resistant RCC cell lines compared to parental cells. Although no specific effect of RAB27B on exosomes was identified in RCC cells, loss-of-function studies demonstrated that knockdown of RAB27B suppressed cell proliferation, migration and invasive activities. Moreover, anti-tumor effects of RAB27B downregulation were also observed in sunitinib-resistant RCC cells. RNA sequence and pathway analysis suggested that the oncogenic effects of RAB27B might be associated with MAPK and VEGF signaling pathways. These results showed that RAB27B is a prognostic marker and a novel therapeutic target in sunitinib-sensitive and -resistant RCCs. Further analyses should improve our understanding of sunitinib resistance in RCC.

The alcohol-abuse drug disulfiram has antitumor effects against diverse cancer types via inhibition of the ubiquitin-proteasome protein nuclear protein localization protein 4 (NPL4). However, the antitumor effects of NPL4 and disulfiram in clear cell renal cell carcinoma (ccRCC) are unclear. Here, we evaluated the therapeutic potential of targeting the ubiquitin-proteasome pathway using disulfiram and RNA interference and investigated the mechanisms underlying disulfiram in ccRCC. According to data from The Cancer Genome Atlas, NPL4 mRNA expression was significantly upregulated in clinical ccRCC samples compared with that in normal kidney samples, and patients with high NPL4 expression had poor overall survival compared with patients with low NPL4 expression. Disulfiram and NPL4 siRNA inhibited ccRCC cell proliferation in vitro, and disulfiram inhibited ccRCC tumor growth in a xenograft model. Synergistic antiproliferative effects were observed for combination treatment with disulfiram and sunitinib in vitro and in vivo. In RCC cells from mice treated with disulfiram and/or sunitinib, several genes associated with serine biosynthesis and aldose reductase were downregulated in cells treated with disulfiram or sunitinib alone and further downregulated in cells treated with both disulfiram and sunitinib. These findings provided insights into the mechanisms of disulfiram and suggested novel therapeutic strategies for RCC treatment.

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited kidney disease with growing multiple cyst formation. We report here a huge ADPKD case of kidney transplantation concomitant with simple nephrectomy through thoracoabdominal approach that allows surgeons to manipulate the renal vessels, the adrenal grand, the trigonal ligament, and the lower pole of the kidney under the wide operative field. Because of the direct recognition of the surgical anatomy, it might be safe and feasible for simple nephrectomy in huge ADPKD patients undergoing concomitant kidney transplantation despite of the wide skin incision required by this approach. Keywords: ADPKD, Thoracoabdominal approach, Kidney transplantation

Bladder cancer (BC) is the fifth most common cancer worldwide and is associated with significant morbidity and mortality. The prognosis of muscle invasive BC is poor, and recurrence is common after radical surgery or chemotherapy. Therefore, new diagnostic methods and treatment modalities are critical. MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate the expression of protein-coding genes by repressing translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs have important roles in the regulation of genes involved in cancer development, progression, and metastasis. The availability of genomewide miRNA expression profiles by deep sequencing technology has facilitated rapid and precise identification of aberrant miRNA expression in BC. Indeed, several miRNAs that are either upregulated or downregulated have been shown to have associations with significant cancer pathways. Furthermore, many miRNAs, including those that can be detected in urine and blood, have been studied as potential noninvasive tumor markers for diagnostic and prognostic purposes. Here, we searched PubMed for publications describing the role of miRNAs in BC by using the keywords “bladder cancer” and “microRNA” on March 1, 2016. We found 374 papers and selected articles written in English in which the level of scientific detail and reporting were sufficient and in which novel findings were demonstrated. In this review, we summarize these studies from the point of view of miRNA-related molecular networks (specific miRNAs and their targets) and miRNAs as tumor markers in BC. We also discuss future directions of miRNA studies in the context of therapeutic modalities.

Este trabalho teve como objetivo compreender se a accountability é, ou não, a razão de ser da Contabilidade. Se a resposta for positiva e corretamente compreendida pelos professores, pesquisadores e profissionais da Contabilidade, poderemos alimentar a esperança de que o nosso status social, político e econômica atingirá brevemente o nível desejado por todos nós, na mesma medida em que o conceito de accountability for aplicado em nosso País, com due diligence. As pesquisas que vêm sendo realizadas há mais de 15 (quinze) anos na Fundação Instituto de Pesquisas Contábeis, Atuariais e Financeiras (Fipecafi) vinculada à FEA/USP, revelam que, no mundo dos negócios públicos e privados, existem basicamente duas formas de accountability, uma delas é de natureza exógena e outra endógena. As duas formas de accountability contribuem para a compreensão do conceito de plena accountability a que se refere o modelo de governança empresarial da International Federation of Accountants (Ifac). A pesquisa de campo que, no início dos anos 90, foi objeto de uma consulta da diretoria para a América do Sul e Caribe do Banco Mundial à Fipecafi, com o objetivo de se mensurar o nível de accountability no Brasil, tanto no setor público como privado, é algo que ainda permanece em aberto, como desafio para os futuros pesquisadores desse tema.

Considera-se que os profissionais da área da Contabilidade e áreas afins devam compreender os termos empregados na área contábil como requisito necessário para o exercício profissional. Pretendeu-se verificar a visão dos estudantes da área e suas representações dos termos contabilidade, custos e investimento. A perspectiva teórico-metodológica, orientadora desta pesquisa, é a Teoria das Representações Sociais, podendo ser entendida como assertivas do senso comum que se elaboram coletivamente nas interações sociais, sujeito-sujeito e sujeito-grupo para dar conta da realidade. Foram coletados 566 depoimentos em diversas regiões do Brasil. Como resultado, verificou-se que não existe consenso na representação social dos termos estudados e se destacaram quatro classes de pensamento. Pode ser observado que os alunos de Contabilidade formavam um bloco que se polarizava à representação dos alunos de Administração e Marketing. Também se posicionam, distintamente, os alunos de primeiros e segundos anos de graduação em relação aos alunos de terceiros e quartos anos. Constatou-se que não existe consenso para os termos investigados. Esta análise tende a mostrar que o primeiro grupo demonstra relacionar os termos à gestão, enquanto o segundo ao operacional. O terceiro demonstra relacionamento ao método contábil e o quarto à fenomenologia contábil. Esses quatro aspectos estão contidos na epistemologia da contabilidade, mas aparecem valorizados de maneiras distintas para os grupos.Professionals from accounting and the related areas are supposed to understand accounting terminology to carry out their professional activities. This study aimed to understand economy accounting and business students' views and representations concerning the words accounting, costs and investment. The theoretical-methodological perspective of this research is the Theory of Social Representations, which can be understood as the common sense statements that are collectively elaborated in social interactions, characterized by person to person and person to group, in order to describe reality. Five hundred sixty-six testimonies were gathered in different Brazilian regions. A polarization could be observed in two different groups: accounting students on the one hand and business and marketing students on the other. Distinct social representations were also observed between first and second-year students on the one hand and third and fourth-year students on the other. A lack of consensus was observed for the analyzed terms. Therefore, the analysis tends to demonstrate that the first group relates the terms with management, while the second group relates them to the operational aspect. The third group establishes a relation with the accounting method, and the fourth with accounting phenomenology. These four aspect are contained in accounting epistemology; but their values are different for distinct groups.

Current genome-wide microRNA (miRNA) expression signature analysis using deep sequencing technologies can drive the discovery of novel cancer pathways regulated by oncogenic and/or tumor suppressive miRNAs. We determined the genome-wide miRNA expression signature in bladder cancer (BC) by deep sequencing technology. A total of ten small RNA libraries were sequenced (five BCs and five samples of histologically normal bladder epithelia (NBE)), and 13,190,619 to 18,559,060 clean small RNA reads were obtained. A total of 933 known miRNAs and 17 new miRNA candidates were detected in this analysis. Among the known miRNAs, a total of 60 miRNAs were significantly downregulated in BC compared with NBE. We also found that several miRNAs, such as miR-1/133a, miR-206/133b, let-7c/miR-99a, miR-143/145 and miR-195/497, were located close together at five distinct loci and constituted clustered miRNAs. Among these clustered miRNAs, we focused on the miR-195/497 cluster because this clustered miRNA had not been analyzed in BC. Transfection of mature miR-195 or miR-497 in two BC cell lines (BOY and T24) significantly inhibited cancer cell proliferation, migration and invasion, suggesting that the miR-195/497 cluster functioned as tumor suppressors in BC. Regarding the genes targeted by the miR-195/497 cluster, the TargetScan algorithm showed that 6,730 genes were putative miR-195/497 targets, and 113 significantly enriched signaling pathways were identified in this analysis. The "Pathways in cancer" category was the most enriched, involving 104 candidate target genes. Gene expression data revealed that 27 of 104 candidate target genes were actually upregulated in BC clinical specimens. Luciferase reporter assays and Western blotting demonstrated that BIRC5 and WNT7A were directly targeted by miR-195/497. In conclusion, aberrant expression of clustered miRNAs was identified by deep sequencing, and downregulation of miR-195/497 contributed to BC progression and metastasis. Tumor suppressive miRNA-mediated cancer pathways provide new insights into the potential mechanisms of BC oncogenesis.

Tendo em vista que a compreensibilidade das informações contábeis é um dos atributos necessários para que a Contabilidade possa servir ao processo decisório, o presente trabalho procura discutir até que ponto os usuários de tais informações conseguem compreender a terminologia empregada na evidenciação contábil. A literatura revela que a preocupação com o aspecto da compreensibilidade na área contábil não é nova, mas nota-se que ela vem aumentando na medida em que o leque de usuários das informações contábeis se amplia, quer seja impulsionado pelo fenômeno da globalização de mercados, quer pelo progresso das tecnologias da informação. Além disso, observa-se que os usuários mais tradicionais, tais como fornecedores, clientes e investidores, tornam-se mais exigentes em relação à quantidade e à qualidade das informações que lhes são oferecidas. Tomando-se por base a literatura corrente e alguns resultados de pesquisas, levanta-se a hipótese de que muitos termos empregados nas demonstrações contábeis não são compreendidos por seus destinatários ou são interpretados de maneira diferente da que se pretendia. Alega-se que uma das prováveis causas desse desencontro entre significados pretendidos e alcançados não reside apenas no uso de termos eminentemente técnicos, mas também no hábito de os contadores atribuírem significados técnicos a palavras que são utilizadas com sentido diferente na linguagem comum. A título de exemplo, cite-se que o usuário tanto pode ignorar o significado contábil de um termo como goodwill, como também atribuir um significado diferente do desejado ao termo depreciação. Se isso pode ocorrer com usuários mais familiarizados com a terminologia contábil, a exemplo de investidores, credores e outros semelhantes, o que pode ser dito em relação aos menos tradicionais, tais como entidades de proteção ambiental, organizações não governamentais voltadas para a defesa dos direitos humanos, ou até mesmo o cidadão comum que, por si próprio, recorra a demonstrações contábeis para conhecer a relação das empresas com o ambiente onde opera? Diante disso, e considerando que a Contabilidade se caracteriza como um processo de comunicação, propõe-se que se utilizem os conceitos da Teoria da Comunicação para desenvolver e aprimorar metodologias que permitam ajustar a terminologia utilizada na evidenciação contábil às características e necessidades de seus usuários. Se a referida Teoria tem sido utilizada com muito êxito em diversos ramos do conhecimento humano, tais como a economia, a psicologia e a biofísica, é provável que a Contabilidade também possa extrair proveito de seu arcabouço conceitual para alcançar maior eficácia no processo de comunicação das informações contábeis.Considering the understandability of accounting information as one of the necessary attributes for Accounting to be able to assist in the decision-making process, this paper discusses to which degree the users of such information manage to understand the terminology used in accounting disclosure. Literature reveals that, although the preoccupation with the understandability aspect in accounting is not new, it is increasing to the extent that the variety of users of accounting information is amplified, whether this is urged by the phenomenon of market globalization, or by the progress of information technology. Besides, it is observed that the most traditional users, such as suppliers, clients and investors, are becoming more demanding in relation to the quantity and quality of the information they are offered. On the basis of current literature and some research results, the hypothesis is brought up that many terms used in financial statements are not understood by the persons they are destined for, or are interpreted in a different way than what was pretended. It is alleged that one of the probable causes of this lack of correspondence between intended and attained meanings lies not only in the use of eminently technical terms, but also in the habit of accountants to attribute technical meanings to words used with a different meaning in common language. As an example, we quote that the user can not only ignore the accounting meaning of a term like goodwill, but can also attribute an unwanted meaning to the term depreciation. If this can occur with those users that are more familiar with accounting terminology, such as, for example, investors, creditors and other similar users, what can be said then about the less traditional users, such as environmental protection entities, non-governmental organizations in defense of human rights, or even the common citizen who, by himself, turns to financial statements to know about the relation between companies and the environment they work in. In view of what was mentioned above, and considering that Accounting is characterized as a communication process, the use of concepts from Communication Theory is proposed, in order to develop and improve methodologies that allow for the adjustment of the terminology used in accounting disclosure to the characteristics and necessities of its users. If the Theory referred to has been used very successfully in various areas of human knowledge, such as economy, psychology and biophysics, it is probable that Accounting will also be able to take advantage of its conceptual framework in order to reach a higher level of efficacy in the accounting information communication process.

Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs). In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa) and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1) and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as 'Pathways in cancer', 'Jak-STAT signaling pathway', and 'Wnt signaling pathway'. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3' UTR of several target genes (such as RAC1, EGFR and EP300) that are components of 'Pathways in cancer'. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.

OBJECTIVE:Genistein is a soy isoflavone that has antitumor activity both in vitro and in vivo. It has been shown that genistein inhibits many type of cancers including prostate cancer (PCa) by regulating several cell signaling pathways and microRNAs (miRNAs). Recent studies suggest that the long non-coding RNAs (lncRNAs) are also involved in many cellular processes. At present there are no reports about the relationship between gensitein, miRNAs and lncRNAs. In this study, we focused on miRNAs, lncRNA that are regulated by genistein and investigated their functional role in PCa. METHOD:Microarray (SurePrint G3 Human GE 8×60K) was used for expression profiling of genistein treated and control PCa cells (PC3 and DU145). Functional assay (cell proliferation, migration, invasion, apoptosis and cell cycle assays) were performed with the PCa cell lines, PC3 and DU145. Both in vitro and in vivo (nude mouse) models were used for growth assays. Luciferase reporter assays were used for binding of miR-34a to HOTAIR. RESULTS:LncRNA profiling showed that HOTAIR was highly regulated by genistein and its expression was higher in castration-resistant PCa cell lines than in normal prostate cells. Knockdown (siRNA) of HOTAIR decreased PCa cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells. CONCLUSIONS:Our results indicated that genistein inhibited PCa cell growth through down-regulation of oncogenic HOTAIR that is also targeted by tumor suppressor miR-34a. These findings enhance understanding of how genistein regulates lncRNA HOTAIR and miR-34a in PCa.

Genistein has been shown to suppress the growth of several cancers through modulation of various pathways. However, the effects of genistein on the regulation of oncogenic microRNA-151 (miR-151) have not been reported. In this study, we investigated whether genistein could alter the expression of oncogenic miR-151 and its target genes that are involved in the progression and metastasis of prostate cancer (PCa). Real-time RT-PCR showed that the expression of miR-151 was higher in PC3 and DU145 cells compared with RWPE-1 cells. Treatment of PC3 and DU145 cells with 25 µM genistein down-regulated the expression of miR-151 compared with vehicle control. Inhibition of miR-151 in PCa cells by genistein significantly inhibited cell migration and invasion. In-silico analysis showed that several genes (CASZ1, IL1RAPL1, SOX17, N4BP1 and ARHGDIA) suggested to have tumor suppressive functions were target genes of miR-151. Luciferase reporter assays indicated that miR-151 directly binds to specific sites on the 3'UTR of target genes. Quantitative real-time PCR analysis showed that the mRNA expression levels of the five target genes in PC3 and DU145 were markedly changed with miR-151 mimics and inhibitor. Kaplan-Meier curves and log-rank tests revealed that high expression levels of miR-151 had an adverse effect on survival rate. This study suggests that genistein mediated suppression of oncogenic miRNAs can be an important dietary therapeutic strategy for the treatment of PCa.

Based on an analysis of the housing market in the Tokyo metropolitan area, this study focuses on the external diseconomies of aging condominiums. It is possible that the quality of the condominium stock deteriorates more rapidly than that of ordinary housing. This deterioration in quality leads to a reduction in the quality of housing services received by residents. Furthermore, this worsening of the residential environment may lead to external diseconomies. We run hedonic models to identify the external diseconomies of aging condominiums in the residential market of the Tokyo metropolitan area. The results of our estimated models indicate that such external diseconomies occur for detached housing in areas where detached houses and condominiums coexist. These external diseconomies exert downward pressure on prices. Specifically, detached housing prices are lowered by around 3.2% for each 1% increase in the proportion of total building floor area in neighborhoods where condominiums were built before 1990. In other words, aging condominiums begin to generate diseconomies in their vicinities approximately 20 years after they were built. [ABSTRACT FROM AUTHOR]