55 research outputs found

    PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro

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    Abstract Introduction Alterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines. Methods Forty-seven human breast cancer and immortalized cell lines representing the known molecular subgroups of breast cancer were treated with PD 0332991 to determine IC50 values. These data were analyzed against baseline gene expression data to identify genes associated with PD 0332991 response. Results Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while nonluminal/basal subtypes were most resistant. Analysis of variance identified 450 differentially expressed genes between sensitive and resistant cells. pRb and cyclin D1 were elevated and CDKN2A (p16) was decreased in the most sensitive lines. Cell cycle analysis showed G0/G1 arrest in sensitive cell lines and Western blot analysis demonstrated that Rb phosphorylation is blocked in sensitive lines but not resistant lines. PD 0332991 was synergistic with tamoxifen and trastuzumab in ER+ and HER2-amplified cell lines, respectively. PD 0332991 enhanced sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade. Conclusions These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991

    Gender and counterproductive work behaviors among police officers

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    At the foundation of this research lies the belief that the sex can directly differentiate the perception of counterproductive behavior at work and also can be a moderator of the influence of different variables on the perception of counterproductive behaviors. The survey research was carried out in June 2017, with the use of Internet-based survey questionnaire (CAWI). There were altogether 198 police officers examined. The hypothesis of the occurrence of the dependence between the sex and the perception of counterproductive behaviors was subjected to verification. The chi-square test of independence and test of significance of differences between means were applied. The conclusions following from the research offer significant implications for elaboration of relevant procedures in the sphere of managing human resources in the police force, among others, with the aim to have the principle of equality of chances and that of equal treatment of women and men respected

    Kano questionnaire as a tool for evaluating qualitative characteristics of educational services: the perspective of loyal and disloyal students

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    The main aim of the research was to identify the attributes of educational service, which affect its quality from the point of view of students. Simultaneously, the authors’ intention was to check whether there appear differences in evaluation of the importance of characteristics of this service between the examined groups of customers, that is the loyal and the disloyal students. The most numerously represented is the category of Must-be attributes. The difference was noted in the case of classification of eleven out of thirty-three examined attributes. As regards the organization of studies, distribution of classes and facilitations, and also requirements set to the didactic personnel, the results of the research point to a lack of differences in the evaluations. The most frequently found differences occur in the assessment of the college’s infrastructure

    Ocena cech jakościowych usługi edukacyjnej z perspektywy lojalnego i nielojalnego studenta szkoły wyższej

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    The article deals with the problem of applying the Kano questionnaire to make an assessment of quality features of an educational service by students. The authors present the usability of the Kano questionnaire for this purpose. The main aim of the research was to identify those attributes of an educational service that influence its quality from the point of view of a student of an institution of higher education. At the same time, the authors intended to examine whether there are differences in the evaluation of the qualities of this service between the groups of the so-called loyal and disloyal students. The survey research proved that there exist statistically significant differences of two proportions in the students’ assessment of the quality attributes of an educational service, while a hierarchization/classification of these attributes in most cases is similar in both of the examined groups.W artykule podjęto temat wykorzystania kwestionariusza Kano do oceny cech jakościowych usługi edukacyjnej przez studentów. Autorki prezentują użyteczność kwestionariusza Kano. Głównym celem badań była identyfikacja atrybutów usługi edukacyjnej, które mają wpływ na jej jakość z punktu widzenia studenta szkoły wyższej. Równocześnie zamiarem autorek było sprawdzenie, czy pomiędzy badanymi grupami studentów tzw. lojalnych i nielojalnych występują różnice w ocenie ważności cech tejże usługi. Badania ankietowe wykazały, że występują statystycznie istotne różnice dwóch proporcji w zakresie oceny cech jakościowych usługi edukacyjnej, natomiast hierarchizacja/klasyfikacja tychże cech w większości przypadków przebiegała podobnie w obu badanych grupach

    Assessment of the presence of pancreatic intraepithelial neoplasia in various diseases of this organ

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    Purpose: Pancreatic intraepithelial neoplasia (PanIN) is one of the most commonly occurring precancerous lesion in pancreas which leads to development of pancreatic ductal adenocarcinoma (PDAC). We assessed the presence and grade of pancreatic intraepithelial neoplasia in the course of various diseases of the pancreas and its correlations with chosen clinicopathological parameters. null Results: A total of 276 foci of PanIN were identified in 94 patients. The most common lesions were PanIN 1a and PanIN 1b which together constituted 68.2 % of all lesions, whereas the PanIN 2 was present in 21.7% and PanIN 3 in 10.1% of patients. No statistical differences were observed in gender tendency for the development of PanINs. There was correlation between age of patients and degree of PanIN (p=0.034). There is no statistical difference in PanIN frequency among patients with pancreatic ductal adenocarcinomas, neuroendocrine tumors, chronic pancreatitis and pancreatic cysts (p=0.592). Conclusions: Our study showed that important factor in development of pancreatic intraepithelial neoplasia is age and the presence of PanIN in nonneoplastic diseases in older people should be included to the group with increased risk of cancer development
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