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1.
Cancer Cell ; 41(12): 2136-2153.e13, 2023 12 11.
Article in English | MEDLINE | ID: mdl-37995682

ABSTRACT

CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation, with downregulation of the subordinate oncogenic network and redistribution to sites close to differentiation genes. In myeloma cells, CCS1477 induces eviction of EP300/CBP from FGFR3, the target of the common (4; 14) translocation, with redistribution away from IRF4-occupied sites to TCF3/E2A-occupied sites. In a subset of patients with relapsed or refractory disease, CCS1477 monotherapy induces differentiation responses in AML and objective responses in heavily pre-treated multiple myeloma. In vivo preclinical combination studies reveal synergistic responses to treatment with standard-of-care agents. Thus, CCS1477 exhibits encouraging preclinical and early-phase clinical activity by disrupting recruitment of EP300/CBP to enhancer networks occupied by critical transcription factors.


Subject(s)
Hematologic Neoplasms , Nuclear Proteins , Humans , Cell Line, Tumor , Transcription Factors , Protein Domains , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/genetics , E1A-Associated p300 Protein
2.
Przegl Epidemiol ; 59(1): 135-45, 2005.
Article in Polish | MEDLINE | ID: mdl-16013419

ABSTRACT

This study aimed at assessing validity and reliability of Social Support Interactions Scale and it's usefulness in evaluation of social support received by elderly people in Poland. Theoretical validity of the scale was evaluated using exploratory factor analysis (principal components method) and confirmatory factor analysis. Reliability was calculated by Cronbach's alpha index and evaluating its internal consistency. Analyses showed some faults in theoretical validity of subscales concerning different dimensions of social support, which decrease their reliability. Nevertheless, scales constituting this survey mostly fulfill Kline's and Nunnaly's criteria, which means that they have acceptable internal consistency. Results confirm acceptable value of Social Support List - Interactions Scale for evaluation of social support received by elderly people in Polish conditions.


Subject(s)
Activities of Daily Living , Geriatric Assessment/methods , Health Status Indicators , Quality of Life , Surveys and Questionnaires/standards , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Outcome Assessment, Health Care , Poland , Regression Analysis , Reproducibility of Results , Social Support
3.
Soz Praventivmed ; 50(3): 177-85, 2005.
Article in English | MEDLINE | ID: mdl-16010817

ABSTRACT

OBJECTIVES: To assess whether socio-economic health differences persist into old age in Poland and if there are SES-related differences in health by age group and gender. METHODS: 528 randomly chosen, not institutionalized elderly people aged 65-85 living in Krakow were interviewed about their socio-economic status (occupation, education, income, house ownership), health status (self-rated health) and quality of life (Cantril's ladder). RESULTS: People with higher level of education and higher occupational status reported significantly better health and better quality of life compared to people who were not as well off. Income level and house ownership had a significant influence on the quality of life of elderly people. In addition, some findings indicate differences in the patterning of health inequalities across particular age and gender groups. CONCLUSION: There are socio-economic differences in health and quality of life among the urban elderly population in Poland which are unfavourable for lower social strata.


Subject(s)
Aged/statistics & numerical data , Health Status , Health Surveys , Socioeconomic Factors , Urban Population/statistics & numerical data , Aged, 80 and over , Female , Humans , Male , Poland , Sex Factors
4.
Croat Med J ; 45(6): 750-6, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15578811

ABSTRACT

AIM: To describe health status and the quality of life among the Polish and Croatian elderly and explore differences between the countries, as well as patterns of gender and age differences. METHODS: Randomly chosen elderly aged 65-85 from Krakow (Poland) and from Zagreb and some smaller towns in Croatia were interviewed on health (self-rated health, physical functioning, mental health, perceived bodily pain, hearing and vision ability, morbidity, functional status, loneliness and depression) and general quality of life. The database (528 and 286 interviews with the Polish and Croatian elderly, respectively) was analyzed using the Mann-Whitney U test, Kruskal-Wallis H test, and general linear model procedure. RESULTS: Significant differences in favor of the Croatian elderly were found in self-rated health and perceived bodily pain (controlled for age, gender, education, and morbidity). The Polish elderly experienced fewer depressive symptoms and reported better vision ability and quality of life in comparison with the Croatian elderly. With some exceptions (hearing and vision ability) the collected data confirmed better health status and quality of life in men in comparison with women in both countries. Significant trends were found in deterioration of health with age. However, the pattern of deteriorating health with age was inconsistent, and more visible among women than among men. Health status results in Poland and Croatia were generally lower in comparison with elderly populations in Western Europe. CONCLUSION: The findings suggest that the broadest possible panel of instruments should be used to describe health within each country and to compare health between the countries. Poor health and quality of life produce a considerable task for public health bodies in Poland and Croatia to equal the standards of the European Union.


Subject(s)
Health Status , Quality of Life , Age Distribution , Aged , Aged, 80 and over , Croatia/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Morbidity , Poland/epidemiology , Sex Distribution , Statistics, Nonparametric
5.
Przegl Epidemiol ; 57(4): 693-702, 2003.
Article in Polish | MEDLINE | ID: mdl-15029845

ABSTRACT

Aim of this study was assessing validity and reliability of Short Form General Health Survey (SF-20) and it's usefulness in evaluation of health status of elderly people in Polish conditions. Study group consisted of 529 randomly chosen elderly (household residents) living in Krakow. Theoretical validity of the test was evaluated using exploratory factor analysis (principal components method). Reliability was calculated by Cronbach's alpha index and by checking if questions forming each sub scale fulfill Kline's criterion. Analysis showed some faults in theoretical validity of scales concerning mental and physical health, which decrease their reliability. Nevertheless, scales constituting this Survey fulfill Kline's and Nunnaly's criterias, which means that they have high internal consistency. Results confirm satisfactory value of SF-20 test as an instrument for evaluation of health of elderly people in Polish conditions.


Subject(s)
Activities of Daily Living , Geriatric Assessment , Health Status Indicators , Quality of Life , Surveys and Questionnaires/standards , Aged , Aged, 80 and over , Feasibility Studies , Female , Geriatric Assessment/methods , Humans , Outcome Assessment, Health Care , Poland , Regression Analysis , Reproducibility of Results
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