Діагностика банкрутства в системі антикризового управління

Розглянуто питання відповідності і значимості діагностики фінансового стану кожної стадії антикризового управління. Діагностику банкрутства визначено як ретроспективне, оперативне і перспективне дослідження господарської діяльності та процесу управління підприємством, направлене на виявлення параметрів кризового розвитку за допомогою реалізації комплексу дослідницьких процедур, виявлення слабких ланок і "вузьких місць".Рассмотрены вопросы соответствия и значимости диагностики каждой стадии антикризисного управления. Диагностика банкротства определена как ретроспективное, оперативное и перспективное исследование хозяйственной деятельности и процесса управления предприятием, направленное на выявление параметров кризисного развития с помощью реализации комплекса исследовательских процедур, выявления слабых зон и «узких мест».The article analyzes issues of adequacy and role of diagnostics in all stage of anti-crisis management. The diagnostics of bankruptcy is defined as a retrospective, operative and prospective study of enterprise’s economic activity and management process that is directed to identification of parameters of crisis development by using comprehensive researches and to finding weak spots and "bottlenecks"

Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome

Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of <11. These results indicate that circulating miRNAs have the potential to be non-invasive biomarkers in dogs with Cushing's syndrome that may contribute to clinical decision making

Whole transcriptome analysis of canine pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia, respectively. Local invasion, concurrent disorders, and metastases prevent surgical removal, which is the most effective treatment to date. Given the current lack of effective medical treatment, there is a need for novel therapeutic strategies. To identify druggable pathways driving PPGL development, we performed RNA sequencing on PPGLs (n = 19) and normal adrenal medullas (NAMs; n = 10) of dogs. Principal component analysis (PCA) revealed that PPGLs clearly clustered apart from NAMs. In total, 4,218 genes were differentially expressed between PPGLs and NAMs. Of these, 232 had a log2 fold change of >3 or < −3, of which 149 were upregulated in PPGLs, and 83 were downregulated. Compared with NAMs, PPGLs had increased expression of genes related to the cell cycle, tumor development, progression and metastasis, hypoxia and angiogenesis, and the Wnt signaling pathway, and decreased expression of genes related to adrenal steroidogenesis. Our data revealed several overexpressed genes that could provide targets for novel therapeutics, such as Ret Proto-Oncogene (RET), Dopamine Receptor D2 (DRD2), and Secreted Frizzled Related Protein 2 (SFRP2). Based on the PCA, PPGLs were classified into 2 groups, of which group 1 had significantly higher Ki67 scores (p = 0.035) and shorter survival times (p = 0.04) than group 2. Increased expression of 1 of the differentially expressed genes between group 1 and 2, pleiotrophin (PTN), appeared to correlate with a more aggressive tumor phenotype. This study has shed light on the transcriptomic profile of canine PPGL, yielding new insights into the pathogenesis of these tumors in dogs, and revealed potential novel targets for therapy. In addition, we identified 2 transcriptionally distinct groups of PPGLs that had significantly different survival times

Whole transcriptome analysis of canine pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia, respectively. Local invasion, concurrent disorders, and metastases prevent surgical removal, which is the most effective treatment to date. Given the current lack of effective medical treatment, there is a need for novel therapeutic strategies. To identify druggable pathways driving PPGL development, we performed RNA sequencing on PPGLs (n = 19) and normal adrenal medullas (NAMs; n = 10) of dogs. Principal component analysis (PCA) revealed that PPGLs clearly clustered apart from NAMs. In total, 4,218 genes were differentially expressed between PPGLs and NAMs. Of these, 232 had a log2 fold change of >3 or < -3, of which 149 were upregulated in PPGLs, and 83 were downregulated. Compared with NAMs, PPGLs had increased expression of genes related to the cell cycle, tumor development, progression and metastasis, hypoxia and angiogenesis, and the Wnt signaling pathway, and decreased expression of genes related to adrenal steroidogenesis. Our data revealed several overexpressed genes that could provide targets for novel therapeutics, such as Ret Proto-Oncogene (RET), Dopamine Receptor D2 (DRD2), and Secreted Frizzled Related Protein 2 (SFRP2). Based on the PCA, PPGLs were classified into 2 groups, of which group 1 had significantly higher Ki67 scores (p = 0.035) and shorter survival times (p = 0.04) than group 2. Increased expression of 1 of the differentially expressed genes between group 1 and 2, pleiotrophin (PTN), appeared to correlate with a more aggressive tumor phenotype. This study has shed light on the transcriptomic profile of canine PPGL, yielding new insights into the pathogenesis of these tumors in dogs, and revealed potential novel targets for therapy. In addition, we identified 2 transcriptionally distinct groups of PPGLs that had significantly different survival times

Information about histopathology and RNA quality of canine mammary tumor tissue.

<p>Information about histopathology and RNA quality of canine mammary tumor tissue.</p

Expression of multiple Wnt ligand- and inhibitor Sfrp1-mRNA.

<p>mRNA expression of Wnt1, Wnt2, Wnt3, Wnt4, Wnt5b, Wnt7a and Sfrp1 in two different passages of cell lines. Target gene expression was normalized to that of a reference gene Rps19. Cell lines were divided in three groups (from left to right): cell lines with high, moderate or absent canonical Wnt activity. * indicates p<0.05, **p<0.01 and nd stands for non-detectable.</p

Association between high canonical Wnt activity and LEF1 expression.

<p>(A) mRNA expression of TCF1, LEF1, TCF3 and TCF4 in two different passages of canine mammary cell lines normalized to the expression of Rps19. (B) β-catenin, LEF1 and Axin2 mRNA expression in CMT-U27 cells that were either non-transfected (control) or transfected with mock control (mock), LEF1 siRNA (LEF1) or β-catenin siRNA (β-catenin). mRNA expression was analyzed 24 h and 48 h post-transfection. (C) Average TOP/FOP ratio in CMT-U27 cells as described in (B). * indicates p<0.05 and **p<0.01 compared to the mock control. (D) Rps19 normalized mRNA expression of LEF1 in a panel of canine mammary tumors (tumor) and normal mammary tissue (normal) from the same dog.</p

Cell line morphology and E-cadherin expression.

<p>(A) Canine mammary cell lines grouped based on their morphology as (partially) rounded cells or spindle cells. (B) Expression of E-cadherin at mRNA (top) and protein (bottom) level. Rps19 and actin expression served as reference mRNA and protein, respectively. Arrow indicates the position of full-length mature E-cadherin protein. Additional E-cadherin protein band present in some of the cell lines represents the unprocessed form of the protein.</p

Inhibition of canonical Wnt activity using porcupine inhibitor IWP-2.

<p>(A) Effect of transient Wnt3a co-transfection on TOP and FOP activities in P114 cells. (B) Effect of IWP-2 treatment on TOP and FOP activities in P114 cells co-transfected with Wnt-3a. (C) Effect of IWP-2 treatment on basal TOP/FOP ratio in CMT1, CMT-U27, CMT9, P114, CHMp, CNMp and CNMm cell lines. TOP/FOP ratio after treatment with 10 µM IWP-2 was tested against the control DMSO treatment. * indicates p<0.05 and **p<0.01.</p