35 results on '"Anna Przybyła"'
Search Results
2. Diagnostics of Mutations in MMR/EPCAM Genes and Their Role in the Treatment and Care of Patients with Lynch Syndrome
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Joanna Sobocińska, Tomasz Kolenda, Anna Teresiak, Natalia Badziąg-Leśniak, Magda Kopczyńska, Kacper Guglas, Anna Przybyła, Violetta Filas, Elżbieta Bogajewska-Ryłko, Katarzyna Lamperska, and Andrzej Mackiewicz
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Lynch syndrome ,hereditary cancer ,colorectal cancer ,MMR ,diagnostics ,IHC ,Medicine (General) ,R5-920 - Abstract
Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a disorder caused by an autosomal dominant heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. Individuals with LS are at an increased risk of developing colorectal and extracolonic cancers, such as endometrial, small bowel, or ovarian. In this review, the mutations involved with LS and their diagnostic methods are described and compared, as are their current uses in clinical decision making. Nowadays, LS diagnosis is based on a review of family medical history, and when necessary, microsatellite instability (MSI) or/and immunohistochemistry (IHC) analyses should be performed. In the case of a lack of MMR protein expression (dMMR) or MSI-H (MSI-High) detection in tumor tissue, molecular genetic testing can be undertaken. More and more genetic testing for LS is based mainly on next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA), which provide better and quicker information about the molecular profile of patients as well as individuals at risk. Testing based on these two methods should be the standard and commonly used. The identification of individuals with mutations provides opportunities for the detection of cancer at an early stage as well as the introduction of proper, more effective treatment, which will result in increased patient survival and reduced costs of medical care.
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- 2020
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3. Whole cell melanoma vaccine genetically modified to stem cells like phenotype generates specific immune responses to ALDH1A1 and long-term survival in advanced melanoma patients
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Eliza Kwiatkowska-Borowczyk, Patrycja Czerwińska, Jacek Mackiewicz, Katarzyna Gryska, Urszula Kazimierczak, Katarzyna Tomela, Anna Przybyła, Anna Karolina Kozłowska, Łukasz Galus, Łukasz Kwinta, Ewelina Dondajewska, Agnieszka Gąbka-Buszek, Monika Żakowska, and Andrzej Mackiewicz
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melanoma ,whole cell melanoma vaccine ,aldh1a1 ,melanoma stem cells ,immunotargeting ,il-6 transsignaling ,hyper-il6 ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Allogeneic whole cell gene modified therapeutic melanoma vaccine (AGI-101H) comprising of two melanoma cell lines transduced with cDNA encoding fusion protein composed of IL-6 linked with the soluble IL-6 receptor (sIL-6R), referred to as H6 was developed. H6 served as a molecular adjuvant, however, it has altered vaccine cells phenotype towards melanoma stem cells (MSC)-like with high activity of aldehyde dehydrogenase isoenzyme (ALDH1A1). AGI-101H was applied in advanced melanoma patients with non-resected and resected disease. In the adjuvant setting, it was combined with surgery in case of recurring metastases, which were surgically removed and vaccination continued. A significant fraction of AGI-101H treated melanoma patients is still alive (11–19 years). Out of 106 living patients, 39 were HLA-A2 positive and were the subject of the study. Immunization of melanoma patients resulted in the generation of cytotoxic CD8+ T cells specific for ALDH1A1, which were detected in circulation by HLA-A0201 MHC dextramers loaded with ALDH1A188-96(LLYKLADLI) peptide. Phenotypically they were central memory CD8+ T cells. Re-stimulation with ALDH1A188-96 ex vivo resulted in IFN-γ secretion and cells degranulation. Following each vaccine dose administration, the number of ALDH1A1-CD8+ T cells increased in circulation and returned to the previous level until next dose injection (one month). ALDH1A1-CD8+ T cells were also found, however in the lower number than in vaccinated patients, in the circulation of untreated melanoma with stage IV but were not found in stage II or III and healthy donors. Specific anti-ALDH1 antibodies were present in treated patients. Long-term survival suggests immuno-targeting of MSC in treated patients.
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- 2018
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4. Quantitative evaluation of trastuzumab deruxtecan pharmacokinetics and pharmacodynamics in mouse models of varying degrees of HER2 expression
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Christina Vasalou, Theresa A. Proia, Laura Kazlauskas, Anna Przybyla, Matthew Sung, Srinivas Mamidi, Kim Maratea, Matthew Griffin, Rebecca Sargeant, Jelena Urosevic, Anton I. Rosenbaum, Jiaqi Yuan, Krishna C. Aluri, Diane Ramsden, Niresh Hariparsad, Rhys D.O. Jones, and Jerome T. Mettetal
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Trastuzumab deruxtecan (T‐DXd; DS‐8201; ENHERTU®) is a human epithelial growth factor receptor 2 (HER2)‐directed antibody drug conjugate (ADC) with demonstrated antitumor activity against a range of tumor types. Aiming to understand the relationship between antigen expression and downstream efficacy outcomes, T‐DXd was administered in tumor‐bearing mice carrying NCI‐N87, Capan‐1, JIMT‐1, and MDA‐MB‐468 xenografts, characterized by varying HER2 levels. Plasma pharmacokinetics (PK) of total antibody, T‐DXd, and released DXd and tumor concentrations of released DXd were evaluated, in addition to monitoring γΗ2AX and pRAD50 pharmacodynamic (PD) response. A positive relationship was observed between released DXd concentrations in tumor and HER2 expression, with NCI‐N87 xenografts characterized by the highest exposures compared to the remaining cell lines. γΗ2AX and pRAD50 demonstrated a sustained increase over several days occurring with a time delay relative to tumoral‐released DXd concentrations. In vitro investigations of cell‐based DXd disposition facilitated the characterization of DXd kinetics across tumor cells. These outputs were incorporated into a mechanistic mathematical model, utilized to describe PK/PD trends. The model captured plasma PK across dosing arms as well as tumor PK in NCI‐N87, Capan‐1, and MDA‐MB‐468 models; tumor concentrations in JIMT‐1 xenografts required additional parameter adjustments reflective of complex receptor dynamics. γΗ2AX longitudinal trends were well characterized via a unified PD model implemented across xenografts demonstrating the robustness of measured PD trends. This work supports the application of a mechanistic model as a quantitative tool, reliably projecting tumor payload concentrations upon T‐DXd administration, as the first step towards preclinical‐to‐clinical translation.
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- 2024
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5. Natural T cell autoreactivity to melanoma antigens: clonally expanded melanoma-antigen specific CD8 + memory T cells can be detected in healthy humans
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Ting Zhang, Andrzej Mackiewicz, Paul V. Lehmann, Anna Przybyła, Ruliang Li, and Diana R. Roen
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Enzyme-Linked Immunospot Assay ,Cancer Research ,T cell ,Immunology ,Autoimmunity ,CD8-Positive T-Lymphocytes ,Biology ,Lymphocyte Activation ,Glycoprotein 100 ,Interferon-gamma ,MART-1 Antigen ,Antigen ,Antigens, Neoplasm ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Interferon gamma ,neoplasms ,Cell Proliferation ,Melanoma-associated antigen ,Monophenol Monooxygenase ,Molecular biology ,Healthy Volunteers ,Clone Cells ,Neoplasm Proteins ,Granzyme B ,medicine.anatomical_structure ,Oncology ,Immunologic Memory ,CD8 ,gp100 Melanoma Antigen ,medicine.drug - Abstract
We used four-color ImmunoSpot® assays, in conjunction with peptide pools that cover the sequence of tyrosinase (Tyr), melanoma-associated antigen A3 (MAGE-A3), melanocyte antigen/melanoma antigen recognized by T cells 1 (Melan-A/MART-1), glycoprotein 100 (gp100), and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) to characterize the melanoma antigen (MA)-specific CD8 + cell repertoire in PBMC of 40 healthy human donors (HD). Tyr triggered interferon gamma (IFN-γ)-secreting CD8 + T cells in 25% of HD within 24 h of antigen stimulation ex vivo. MAGE-A3, Melan-A/MART-1, and gp100 also induced recall responses in 10%, 7.5%, and 2.5% of HD, respectively. At this time point, these CD8 + T cells did not yet produce GzB (granzyme B). However, they engaged in GzB production after 72 h of antigen stimulation. By this 72-h time point, 57.5% of the HD responded to at least one, and typically several, of the MA. A closer characterization of the Tyr-specific CD8 + T cell repertoire indicated that it was low-affinity, and to primarily entail a stem cell-like subpopulation. Collectively, our data reveal pre-existing endogenous T cell immunity against melanoma antigens in healthy donors, and analogous to natural autoantibodies, we have termed this "natural T cell autoreactivity".
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- 2019
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6. Functional T Cell Reactivity to Melanocyte Antigens Is Lost during the Progression of Malignant Melanoma, but Is Restored by Immunization
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Anna Przybyła, Greg A. Kirchenbaum, Łukasz Galus, Andrzej Mackiewicz, Paul V. Lehmann, Ting Zhang, Alexander A. Lehmann, and Jacek Mackiewicz
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0301 basic medicine ,Cancer Research ,T cell ,Cell ,medicine.disease_cause ,CD8+ T cells ,lcsh:RC254-282 ,Article ,Autoimmunity ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,medicine ,melanoma ,Cytotoxic T cell ,neoplasms ,business.industry ,ELISPOT ,Melanoma ,genetic whole-cell therapeutic melanoma vaccine (AGI-101H) ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,medicine.anatomical_structure ,melanoma antigens ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,business ,CD8 - Abstract
Healthy human subjects develop spontaneous CD8+ T cell responses to melanoma associated antigens (MA) expressed by normal melanocytes, such as Tyrosinase, MAGE-A3, Melan/Mart-1, gp100, and NY-ESO-1. This natural autoimmunity directed against melanocytes might confer protection against the development of malignant melanoma (MM), where MA are present as overexpressed tumor-associated antigens. Consistent with this notion we report here that functional T cell reactivity to MA was found to be significantly diminished to MAGE-A3, Melan-A/Mart-1, and gp100 in untreated MM patients. Three lines of evidence suggest that the MA-reactive T cells present in healthy subjects undergo exhaustion once MM establishes itself. First, only the MA-specific T cell reactivity was affected in the MM patients, that to third party recall antigens was not. Second, in these patients, the residual MA-specific T cells, unlike third party antigen reactive T cells, were functionally impaired, showing a diminished per cell IFN-&gamma, productivity. Third, we show that immunization with MA restored natural CD8+ T cell autoimmunity to MA in 85% of the MM patients. The role of natural T cell autoimmunity to tumor-associated MA is discussed based on discrete levels of T cell activation thresholds.
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- 2021
7. Diagnostics of Mutations in MMR/EPCAM Genes and Their Role in the Treatment and Care of Patients with Lynch Syndrome
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Anna Teresiak, Katarzyna Lamperska, Kacper Guglas, Anna Przybyła, Andrzej Mackiewicz, Elzbieta Bogajewska-Rylko, Natalia Badziąg-Leśniak, Violetta Filas, Tomasz Kolenda, Magda Kopczyńska, and Joanna Sobocińska
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Colorectal cancer ,Clinical Biochemistry ,colorectal cancer ,Review ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Internal medicine ,diagnostics ,Medicine ,Multiplex ligation-dependent probe amplification ,MSI ,Genetic testing ,lcsh:R5-920 ,medicine.diagnostic_test ,business.industry ,Cancer ,Microsatellite instability ,medicine.disease ,MMR ,Lynch syndrome ,digestive system diseases ,MLPA ,030104 developmental biology ,hereditary cancer ,030220 oncology & carcinogenesis ,NGS ,DNA mismatch repair ,lcsh:Medicine (General) ,business ,IHC - Abstract
Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a disorder caused by an autosomal dominant heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. Individuals with LS are at an increased risk of developing colorectal and extracolonic cancers, such as endometrial, small bowel, or ovarian. In this review, the mutations involved with LS and their diagnostic methods are described and compared, as are their current uses in clinical decision making. Nowadays, LS diagnosis is based on a review of family medical history, and when necessary, microsatellite instability (MSI) or/and immunohistochemistry (IHC) analyses should be performed. In the case of a lack of MMR protein expression (dMMR) or MSI-H (MSI-High) detection in tumor tissue, molecular genetic testing can be undertaken. More and more genetic testing for LS is based mainly on next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA), which provide better and quicker information about the molecular profile of patients as well as individuals at risk. Testing based on these two methods should be the standard and commonly used. The identification of individuals with mutations provides opportunities for the detection of cancer at an early stage as well as the introduction of proper, more effective treatment, which will result in increased patient survival and reduced costs of medical care.
- Published
- 2020
8. Wound fluids affect miR-21, miR-155 and miR-221 expression in breast cancer cell lines, and this effect is partially abrogated by intraoperative radiation therapy treatment
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Katarzyna Kulcenty, Mateusz Wichtowski, Dawid Murawa, Karolina Zaleska, Wiktoria Maria Suchorska, Anna Przybyła, and Andrzej Mackiewicz
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,surgical wound fluids ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Cancer stem cell ,Internal medicine ,medicine ,Breast-conserving surgery ,skin and connective tissue diseases ,intraoperative radiotherapy ,Intraoperative radiation therapy ,Oncogene ,microRNA ,business.industry ,Cancer ,Articles ,medicine.disease ,Radiation therapy ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,Carcinogenesis - Abstract
Breast cancer is the most common malignant disease occurring in women. Conservative breast cancer surgery followed by radiation therapy is currently the standard treatment for this type of cancer. The majority of metastases occur within the scar, which initiated a series of studies. As a result, clinical trials aimed to assess whether localized radiotherapy, as intraoperative radiotherapy (IORT), may more effective in inhibiting the formation of local recurrence compared with the standard postoperative whole breast radiotherapy. The present study determined the role of postoperative wound fluids (WFs) from patients diagnosed with breast cancer subsequent to breast conserving surgery or breast conserving surgery followed by IORT on the expression of three microRNAs (miRNAs), consisting of miR-21, miR-155 and miR-221, in distinct breast cancer cell lines that represent the general subtypes of breast cancer. It was determined that the miRNAs responsible for breast cancer progression, induction of tumorigenesis and enrichment of the cancer stem cell phenotype, which is responsible for resistance to tumor therapy, were highly upregulated in the human epidermal growth factor receptor 2-positive breast cancer SK-BR-3 cell line following stimulation with WFs. It is worth emphasizing, that those changes were more significant in WFs collected from patients after surgery alone. The BT-549 cell line showed altered expression only of miR-155 following incubation with WFs. Notably, this change was not associated with IORT. Additionally, it was indicated that both WFs and RT-WF strongly downregulated the expression of miR-21, miR-155 and miR-221 in basal/epithelial and luminal subtypes of breast cancer. It was concluded that the present study contributes to an increased understanding of the role of surgical WFs and IORT treatment in the regulation of miRNA expression. This may enable the development of the current knowledge of breast cancer biology subsequent to IORT treatment and substantially to improve the therapy in the future.
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- 2017
9. Effect of surgical wound fluids after intraoperative electron radiotherapy on the cancer stem cell phenotype in a panel of human breast cancer cell lines
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Wiktoria Maria Suchorska, Dawid Murawa, Karolina Zaleska, and Anna Przybyła
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cancer stem cells ,0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,surgical wound fluids ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Cancer stem cell ,medicine ,intraoperative radiotherapy ,Tumor microenvironment ,Cluster of differentiation ,biology ,CD44 ,Cancer ,Surgical wound ,Articles ,medicine.disease ,Radiation therapy ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research - Abstract
The wound healing process after surgery alters the area surrounding the original tumor and around the scar, and the modified microenvironment is more favorable for tumor recurrence. Intraoperative radiotherapy (IORT) is one of the more novel strategies in breast cancer (BC) treatment. Irradiation during surgery has effects on the tumor microenvironment, abrogating the proliferative cascade induced by surgical wound healing. The aim of the present study was to determine the effect of surgical wound fluids from IOERT treatment (RT-WF) compared with wound fluids from conservative-breast surgery only (WF) on the cancer stem cell phenotype in a panel of BC cell lines. Post-operative wound fluids were derived from patients with BC who underwent a tumor resection (quadrantectomy) plus intraoperative electron radiotherapy using a single dose of ≤10 Gy on the tumor bed and surrounding tissues, or from those who underwent a tumor resection without IOERT. Cell lines were incubated with 10% wound fluids, and after 4 days, the cluster of differentiation (CD)44+/CD24−/low phenotype and aldehyde dehydrogenase 1 (ALDH1) activity were determined by flow cytometry. The two types of fluid each affected the CD44+/CD24−/low phenotype. The results varied markedly between each cell line, even for the same histological subtypes. RT-WF decreased the CD44+/CD24−/low populations in the basal-like BT-549 and MDA-MB-468 cell lines, whereas in the luminal type MCF7 cell line, the two fluids inhibited these populations. The HER-OE subtypes harbored a minimal CD44+/CD24−/low population, but the growth of SK-BR-3 was stimulated by the two post-operative fluids. WF exhibited a stronger effect on ALDH1 activity compared with RT-WF. The stimulatory effect was dependent on the histological subtype of the cell line and the strongest dependence was observed in luminal subtypes characterized by low dehydrogenase activity in the control group. The present results enable a better understanding of the mechanism of recurrence and metastases following BC surgery. With respect to histological phenotype, its effect on tumor progression, either local or systemic, strongly suggests the requirement for further research and clinical validation.
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- 2016
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10. Direct Detection of T- and B-Memory Lymphocytes by ImmunoSpot® Assays Reveals HCMV Exposure that Serum Antibodies Fail to Identify
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Alexander A. Lehmann, Tobias M. Nowacki, Stefanie Kuerten, Anna Przybyła, Fredrik Terlutter, Ruliang Li, Richard Caspell, Ting Zhang, and Paul V. Lehmann
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0301 basic medicine ,Human cytomegalovirus ,viruses ,CD4 T cells ,CD8 T cells ,Peripheral blood mononuclear cell ,Virus ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Medizinische Fakultät ,serum antibodies ,Medicine ,Cytotoxic T cell ,ddc:610 ,human cytomegalovirus (HCMV) ,enzyme-linked ImmunoSpot assay ,ELISPOT ,B cells ,biology ,business.industry ,virus diseases ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,030104 developmental biology ,Immunology ,biology.protein ,Antibody ,business ,CD8 ,030215 immunology - Abstract
It is essential to identify donors who have not been infected with human cytomegalovirus (HCMV) in order to avoid transmission of HCMV to recipients of blood transfusions or organ transplants. In the present study, we tested the reliability of seronegativity as an indicator for the lack of HCMV exposure in healthy human blood donors. Eighty-two HCMV seronegative individuals were identified, and their peripheral blood mononuclear cells (PBMC) were tested in ImmunoSpot® assays for the presence of HCMV-specific T- and B-memory lymphocytes. Eighty-two percent (67 of 82) of these HCMV seronegative individuals featured at least one memory cell that was lineage specific for HCMV, with the majority of these subjects possessing CD4+ and CD8+ T cells, as well as B cells, providing three independent lines of evidence for having developed immunity to HCMV. Only 15 of these 82 donors (18%) showed neither T- nor B-cell memory to HCMV, consistent with immunological naïveté to the virus. The data suggest that measurements of serum antibodies frequently fail to reveal HCMV exposure in humans, which may be better identified by direct detection of HCMV-specific memory lymphocytes.
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- 2018
11. Analysis of sequence variants in the 3'UTR of CDKN2A gene in melanoma patients
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Andrzej Mackiewicz, Katarzyna Lamperska, and Anna Przybyła
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Genetics ,Regulation of gene expression ,Original Paper ,business.industry ,Three prime untranslated region ,Melanoma ,Cancer ,medicine.disease ,Exon ,CDKN2A ,Oncology ,Gene expression ,melanoma ,Medicine ,Radiology, Nuclear Medicine and imaging ,3'UTR ,business ,polymorphisms ,Sequence (medicine) - Abstract
Background The 3'UTR region plays a crucial role in regulating gene expression at posttranscriptional levels. Any changes in sequence in this region can cause numerous pathologies and can also lead to tumour development. The most common changes reported in in the CDKN2A gene are the 148Ala/Thr in exon 2 and 500C>G and 540C>T in the 3'UTR region. They are suspected of having a great impact on cancer progression. Since the role of these sequence variants in the Polish population in the development of melanoma has not been confirmed, the importance of 3'UTR polymorphisms in the regulation of gene expression was tested. Material and methods First, genetic analysis in a group of 285 melanoma patients was performed and the obtained results were correlated with the clinical course of melanoma. Then vectors carrying 3'UTR sequence variants were prepared and the level expression of the reported gene was measured. Results Within this study no correlation between the presence of 148Ala/Thr polymorphism and cancer in the family was observed. There was a correlation between the presence of this polymorphism and breast cancer and melanoma in the same patient. There was no correlation between 500C>G polymorphism and tumour localisation, age of diagnosis, and type of cancer in patients’ family, but a correlation between the percentage of patients dying and the 500C>G variant was observed. Conclusion The results of functional tests indicated that the presence of polymorphism in the 3'UTR region of the CDKN2A gene resulted in changes in the level of reporter gene expression.
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- 2015
12. Targeting the Hippo Pathway in Cutaneous Melanoma
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Urszula Kazimierczak, Anna Przybyla, Marianna Smielowska, Tomasz Kolenda, and Andrzej Mackiewicz
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cutaneous melanoma ,Hippo pathway ,therapeutic targets ,Cytology ,QH573-671 - Abstract
Melanoma is the most aggressive form of skin cancer. In the advanced stage of development, it is resistant to currently available therapeutic modalities. Increased invasiveness and metastatic potential depend on several proteins involved in various signal transduction pathways. Hippo signaling plays a vital role in malignant transformation. Dysfunctions of the Hippo pathway initiate the expression of tumor growth factors and are associated with tumor growth and metastasis formation. This review summarizes the recent achievements in studying the role of the Hippo pathway in melanoma pathogenesis and points to the potential specific targets for anti-melanoma therapy.
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- 2024
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13. Oncogenic BRAF mutations and p16 expression in melanocytic nevi and melanoma in the Polish population
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Andrzej Mackiewicz, Ewelina Dondajewska, Patrycja Czerwińska, Małgorzata Mackiewicz-Wysocka, Andrzej Marszałek, Elżbieta Bogajewska, Violetta Filas, Agata Kubicka, Tomasz Kolenda, and Anna Przybyła
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0301 basic medicine ,lcsh:Internal medicine ,p16 ,Dermatology ,Polish population ,BRAF ,03 medical and health sciences ,CDKN2A ,0302 clinical medicine ,In vivo ,Proliferation rate ,medicine ,lcsh:Dermatology ,melanoma ,Immunology and Allergy ,lcsh:RC31-1245 ,skin and connective tissue diseases ,neoplasms ,Original Paper ,integumentary system ,business.industry ,Melanoma ,lcsh:RL1-803 ,medicine.disease ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,nevi ,Cancer research ,Immunohistochemistry ,Skin melanoma ,business ,Melanocyte proliferation ,Ki67 - Abstract
Introduction: Twenty-five – fifty percent of skin melanomas arise from nevi. Melanocyte proliferation is activated by BRAF V600E , then is arrested, but single nevi transform to melanomas. p16 controls arrest, and p16 loss may promote transformation. Aim : To analyze BRAF V600E , p16 expression and melanocyte proliferation in dermal, compound and dysplastic nevi, cells of primary and metastatic melanoma in the Polish population. Material and methods : One hundred and thirty-two nevi (dermal, compound, dysplastic) and 41 melanomas (in situ, primary, metastatic) were studied. BRAF was assessed by cobas® 4800 BRAFV600 Mutation Test, High Resolution Melting Assay validated with: pyrosequencing and immunohistochemistry. p16 and Ki67 expression was analyzed by IHC. Results : Eighty-two percent of nevi and 57% of melanomas display BRAF V600E expression. Most dermal and compound nevi had > 50% of p16(+) cells. BRAF V600E dysplastic nevi had a low number of p16(+) cells. Nevi without BRAF V600E (WT), had 90% of cells p16(+). In 60% of in situ and primary melanomas, there was a low number of cells of p16(+). Fifty percent of WT metastatic melanoma and 33% of BRAF V600E showed a high level of p16. The number of Ki67(+) cells in dysplastic nevi was very low. In 25% of BRAF V600E melanomas in situ and 55% of WT, > 10% cells were Ki67(+). All BRAF V600E primary melanomas and 66% of WT had > 10% Ki67(+) cells. Twenty percent of BRAF V600E and WT metastases had > 10% of Ki67(+), however, 62% of BRAF V600E and 32% of WT samples had > 50% of Ki67(+) cells. Conclusions : BRAF V600E and p16 are more frequent in nevi than in melanoma in vivo. A significantly higher p16 expression was observed in mutated nevi than in WT, while in melanoma it was just the opposite. The proliferation rate of melanoma cells negatively correlated with p16 expression.
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- 2017
14. Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells
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Stefanie Kuerten, Anna Przybyła, Paul V. Lehmann, and Andrea Duechting
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0301 basic medicine ,immune monitoring ,T cells ,Biology ,Article ,03 medical and health sciences ,Interleukin 21 ,0302 clinical medicine ,Medizinische Fakultät ,CD4 cells ,Cytotoxic T cell ,ddc:610 ,IL-2 receptor ,Antigen-presenting cell ,lcsh:QH301-705.5 ,Interleukin 3 ,CD40 ,multiplexing ,ELISPOT ,General Medicine ,Natural killer T cell ,Cell biology ,030104 developmental biology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,cytokine kinetics ,Interleukin 12 ,biology.protein - Abstract
During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively. Traditionally, these cytokines are measured within 6 h in flow cytometry. We show here that 6 h of stimulation is sufficient to detect peptide-induced production of IFN-γ, but 24 h are required to reveal the full frequency of protein antigen-specific Th1 cells. Also the detection of IL-2 producing Th1 cells requires 24 h stimulation cultures. Measurements of IL-4 producing Th2 cells requires 48-h cultures and 96 h are required for frequency measurements of IL-5 and IL-17 secreting T cells. Therefore, accounting for the differential secretion kinetics of these cytokines is critical for the accurate determination of the frequencies and ratios of antigen-specific Th1, Th2, and Th17 cells.
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- 2017
15. Improvement of distal symmetrical polyneuropathy in patient with AIDS after switch from protease inhibitor containing antiretroviral treatment to tenofovir disoproxil fumarate, emtricitabine and rilpivirine (EVIPLERA®) therapy – Case report
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Anna Przybyła, Justyna Stempkowska, Sławomir Kiciak, and Dariusz Bielec
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medicine.medical_specialty ,Epidemiology ,business.industry ,virus diseases ,Lopinavir ,Pharmacology ,medicine.disease ,Emtricitabine ,Gastroenterology ,Esophageal candidiasis ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,immune system diseases ,Internal medicine ,Rilpivirine ,medicine ,Protease inhibitor (pharmacology) ,Ritonavir ,business ,Polyneuropathy ,Viral load ,medicine.drug - Abstract
In this paper we present a 29-year-old male patient with AIDS stage C3 according to CDC (esophageal candidiasis). He received combined antiretroviral therapy (cART) with lopinavir/ritonavir and tenofovir disoproxil fumarate/emtricitabine. Almost 2 log reduction of viral load was observed after 1 month of cART, but the patient developed distal symmetrical polyneuropathy. Therapy was switched to tenofovir disoproxil fumarate/emtricitabine/rilpivirine (EVIPLERA ® ). During this therapy HIV-RNA became undetectable, CD4 T cell count increased and distal symmetrical polyneuropathy symptoms improved and then disappeared completely. Therapy was well tolerated and no laboratory abnormalities were observed.
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- 2015
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16. Water-like behavior of 1,2-ethanediol in binary mixtures with pyridine and its methyl derivatives: Thermodynamic excesses and the O–H⋯N bonds energy
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Anna Przybyła, Szymon Bacior, Wojciech Marczak, Piotr Lodowski, and Piotr Kubica
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chemistry.chemical_compound ,Volume (thermodynamics) ,Hydrogen bond ,Chemistry ,Inorganic chemistry ,Pyridine ,General Physics and Astronomy ,Liquid phase ,Molecule ,Physical and Theoretical Chemistry ,Medicinal chemistry - Abstract
The molecule of 1,2-ethanediol, like that of water, is capable of forming two hydrogen bonds as a donor of protons. Consequently, the complexes of pyridine and its methyl derivatives with ethanediol may associate in the liquid phase in a similar way as those with water. The association contributes to the excess molar expansion making its isotherms W-shaped for the mixtures with 2-methylpyridine and 2,6-dimethylpyridine. Negative excesses of volume and compression are correlated with the association energies of the 1:1 amine–ethanediol complexes. They increase in the order: pyridine
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- 2011
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17. Reagent Tracker Dyes Permit Quality Control for Verifying Plating Accuracy in ELISPOT Tests
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Zoltán Megyesi, Alexander A. Lehmann, Anna Przybyła, and Paul V. Lehmann
- Subjects
0301 basic medicine ,education.field_of_study ,RT dyes ,Computer science ,ELISPOT ,Population ,T cells ,antigen screening ,ImmunoSpot® ,determinant mapping ,CD4 cells ,CD8 cells ,audit trails for ELISPOT ,regulated ELISPOT ,chemical and pharmacologic phenomena ,General Medicine ,Immune monitoring ,Article ,03 medical and health sciences ,030104 developmental biology ,Antigen ,Immunology ,T cell immunity ,education - Abstract
ELISPOT assays enable the detection of the frequency of antigen-specific T cells in the blood by measuring the secretion of cytokines, or combinations of cytokines, in response to antigenic challenges of a defined population of PBMC. As such, these assays are suited to establish the magnitude and quality of T cell immunity in infectious, allergic, autoimmune and transplant settings, as well as for measurements of anti-tumor immunity. The simplicity, robustness, cost-effectiveness and scalability of ELISPOT renders it suitable for regulated immune monitoring. In response to the regulatory requirements of clinical and pre-clinical immune monitoring trials, tamper-proof audit trails have been introduced to all steps of ELISPOT analysis: from capturing the raw images of assay wells and counting of spots, to all subsequent quality control steps involved in count verification. A major shortcoming of ELISPOT and other related cellular assays is presently the lack of audit trails for the wet laboratory part of the assay, in particular, the assurance that no pipetting errors have occurred during the plating of antigens and cells. Here, we introduce a dye-based reagent tracking platform that fills this gap, thereby increasing the transparency and documentation of ELISPOT test results.
- Published
- 2018
- Full Text
- View/download PDF
18. Plasma IL-10 dynamics in patients with chronic hepatitis C
- Author
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Roma Modrzewska, Hanna Fota-Markowska, and Anna Przybyła
- Subjects
Pharmacology ,Interleukin 10 ,Chronic hepatitis ,business.industry ,Immunology ,Medicine ,In patient ,General Medicine ,business ,Molecular Biology ,Biochemistry - Published
- 2008
- Full Text
- View/download PDF
19. Serum Bcl-2 level dynamics in acute EBV primary infection
- Author
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Przemysław Łodej, Anna Przybyła, Joanna Wielgosz, Hanna Fota-Markowska, and Kamila Latoś
- Subjects
Pharmacology ,Primary (chemistry) ,business.industry ,Dynamics (mechanics) ,Medicine ,General Medicine ,business ,Molecular Biology ,Biochemistry ,Virology - Published
- 2008
- Full Text
- View/download PDF
20. The CDKN2a common variants: 148 Ala/Thr and 500 C/G in 3' UTR, and their association with clinical course of melanoma
- Author
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Witold Kycler, Anna Przybyła, Katarzyna Lamperska, and Andrzej Mackiewicz
- Subjects
Adult ,Male ,Threonine ,Untranslated region ,Skin Neoplasms ,Biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,CDKN2A ,medicine ,Humans ,Coding region ,Survivors ,3' Untranslated Regions ,Melanoma ,neoplasms ,Gene ,Cyclin-Dependent Kinase Inhibitor p16 ,Polymorphism, Single-Stranded Conformational ,Aged ,Genetics ,Alanine ,Polymorphism, Genetic ,Three prime untranslated region ,Genetic Variation ,DNA, Neoplasm ,Middle Aged ,medicine.disease ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,Amino Acid Substitution ,chemistry ,Female ,Gene polymorphism ,DNA - Abstract
Changes in CDKN2a gene are known to be linked with sporadic melanoma and hereditary predisposition to this cancer. In the Polish population mutations in the coding region of the CDKN2a gene are rather rare, therefore the attention has been focused on polymorphisms and alterations in uncoding regions such as 3' UTR. The aim of this study was to analyze two common polymorphisms, Ala148Thr and 500 C/G, and correlate them with the clinical course of melanoma. DNA from 285 patients was analyzed and found polymorphisms were correlated with the clinical parameters employing statistical methods. The obtained results allow us to conclude: (i) survival times of 500 C/G carriers vs. cumulating proportion surviving was not statistically significant; (ii) CDKN2a polymorphism 500 C/G correlated with Ala148Thr; (iii) no correlation was observed between the 500 C/G polymorphism and age of diagnosis, localization of primary melanoma and survival time; (iv) we did not find correlation between 500 C/G and type of cancer in the family; (v) changes in the CDKN2a gene were not found in patients with second cancer.
- Published
- 2007
- Full Text
- View/download PDF
21. A Positive Control for Detection of Functional CD4 T Cells in PBMC: The CPI Pool
- Author
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Andrea Duechting, Stefanie Kuerten, Annemarie Schiller, Ruliang Li, Ting Zhang, Paul V. Lehmann, Anna Przybyła, and Srividya Sundararaman
- Subjects
0301 basic medicine ,immune monitoring ,CD4 cell function ,Biology ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Medizinische Fakultät ,Interferon ,medicine ,ddc:610 ,PBMC quality assessment ,PBMC cryopreservation ,ELISPOT ,ImmunoSpot ,Antigen-presenting cell ,lcsh:QH301-705.5 ,Antigen processing ,General Medicine ,Mycoplasma ,Virology ,030104 developmental biology ,lcsh:Biology (General) ,CD8 ,030215 immunology ,medicine.drug - Abstract
Testing of peripheral blood mononuclear cells (PBMC) for immune monitoring purposes requires verification of their functionality. This is of particular concern when the PBMC have been shipped or stored for prolonged periods of time. While the CEF (Cytomegalo-, Epstein-Barr and Flu-virus) peptide pool has become the gold standard for testing CD8 cell functionality, a positive control for CD4 cells is so far lacking. The latter ideally consists of proteins so as to control for the functionality of the antigen processing and presentation compartments, as well. Aiming to generate a positive control for CD4 cells, we first selected 12 protein antigens from infectious/environmental organisms that are ubiquitous: Varicella, Influenza, Parainfluenza, Mumps, Cytomegalovirus, Streptococcus, Mycoplasma, Lactobacillus, Neisseria, Candida, Rubella, and Measles. Of these antigens, three were found to elicited interferon (IFN)-γ-producing CD4 cells in the majority of human test subjects: inactivated cytomegalo-, parainfluenza-, and influenza virions (CPI). While individually none of these three antigens triggered a recall response in all donors, the pool of the three (the ‘CPI pool’), did. One hundred percent of 245 human donors tested were found to be CPI positive, including Caucasians, Asians, and African-Americans. Therefore, the CPI pool appears to be suitable to serve as universal positive control for verifying the functionality of CD4 and of antigen presenting cells.
- Published
- 2017
- Full Text
- View/download PDF
22. The anti-cancer actions of O6-methylguanine-DNA-methyltransferase in relation to colon polyps
- Author
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Witold Kycler, Cezary Łoziński, Andrzej Mackiewicz, Anna Teresiak-Mańczak, Konstanty Korski, Katarzyna Lamperska, Anna Przybyła, and Zefiryn Cybulski
- Subjects
Male ,Pathology ,medicine.medical_specialty ,DNA Repair ,Genotype ,DNA repair ,Colorectal cancer ,Colon ,DNA methyltransferase ,Genetic analysis ,Polymerase Chain Reaction ,O(6)-Methylguanine-DNA Methyltransferase ,Polyps ,otorhinolaryngologic diseases ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic variability ,neoplasms ,Alleles ,Pharmacology ,Polymorphism, Genetic ,O6-methylguanine ,business.industry ,Smoking ,Age Factors ,Cancer ,General Medicine ,medicine.disease ,digestive system diseases ,Colon polyps ,surgical procedures, operative ,Case-Control Studies ,Cancer research ,Female ,business - Abstract
Genetic variability in DNA repair genes may contribute to differences in DNA repair capacity and susceptibility to colon polyps and cancer. In this study, we examined the role of MGMT polymorphisms in colon polyps formation.PCR-SSCP analysis was performed included 254 patients with colon polyps and 330 controls.The homozygous F84F genotype was significantly more prevalent in study group than in controls. The polymorphic allele 84F was more frequent appeared in group of older patients and in group of smoking patients. On the other hand, there were no association between 84F and gender, size of polyps, cancer family history.We concluded that high frequency of 84F allele in the group of patients may suggest the role of the MGMT variant in colon polyps etiology.
- Published
- 2013
23. WITHDRAWN: 'Volume effects for binary mixtures of propane-1,2-diol with methanol, propan-1-ol, hexan-1-ol, octan-1-ol, or nonan-1-ol at temperatures (293.15 to 318.15) K'
- Author
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Anna Przybyła and Edward Zorębski
- Subjects
Molar ,Diol ,Analytical chemistry ,Thermodynamics ,Limiting ,Atmospheric temperature range ,Atomic and Molecular Physics, and Optics ,chemistry.chemical_compound ,Molar volume ,Volume (thermodynamics) ,chemistry ,Propane ,General Materials Science ,Methanol ,Physical and Theoretical Chemistry - Abstract
Values of the density for binary mixtures of propane-1,2-diol with methanol, propan-1-ol, hexan-1-ol, octan-1-ol, or nonan-1-ol were measured over the entire composition range and within the temperature range from (293.15 to 318.15) K by means of a vibrating tube densimeter. The excess molar volumes and limiting excess partial molar volumes were calculated. The Redlich–Kister polynomials were fitted to the results and smooth representations of the results are presented. The negative values of the excess molar volumes over the entire composition and temperature ranges are observed in the case of methanol and propan-1-ol. In the cases of hexan-1-ol, octan-1-ol, and nonan-1-ol, positive values of the excess molar volumes over the entire composition and temperature ranges are observed. The effect of temperature is discussed qualitatively.
- Published
- 2012
- Full Text
- View/download PDF
24. Volumetric properties of binary mixtures of 2,4,6-trimethylpyridine with 1,2-ethanediol, methanol, and water, and the association energies of the O-H...N bonded complexes
- Author
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Anna Przybyła, Piotr Lodowski, and Wojciech Marczak
- Subjects
Hydrogen-bonded complexes ,Aqueous solution ,Hydrogen bond ,Diol ,Liquid phase ,Condensed Matter Physics ,Association energy ,Medicinal chemistry ,chemistry.chemical_compound ,Molar volume ,chemistry ,Molecule ,Methanol ,Bond energy - Abstract
2,4,6-Trimethylpyridine forms 1:1 complexes with methanol, 1,2-ethanediol, and water due to the O–H· · ·N bonds. The association energy of the complexes was calculated using MP2 and DFT methods. The complexes with 1,2-ethanediol and water aggregate in the liquid phase as a result of the O–H· · ·O bonds. In spite of the higher O–H· · ·N bond energy, the aggregation of the ethanediolic complexes is less pronounced than that of the aqueous ones. That is probably caused by the weaker induction effect due to the C–C chain separating the hydroxyl groups in the diol molecule. Aggregation is impossible in the methanolic system, because of the lack of proton-donating functional groups. Differences in the hydrogen bond energy and in the ability to aggregate are manifested in the volumetric properties of the mixtures.
- Published
- 2012
25. The influence of cardiac resynchronization therapy on selected inflammatory markers and aldosterone levels in patients with chronic heart failure
- Author
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Anna, Przybyła, Danuta, Czarnecka, Aleksander, Kusiak, Jerzy, Wiliński, Tomasz, Sondej, Marek, Jastrzebski, and Kalina, Kawecka-Jaszcz
- Subjects
Heart Failure ,Male ,Interleukin-6 ,Interleukin-18 ,Cardiac Resynchronization Therapy ,C-Reactive Protein ,Treatment Outcome ,Chronic Disease ,Humans ,Female ,Prospective Studies ,Inflammation Mediators ,Aldosterone ,Biomarkers ,Aged - Abstract
The aim of the study was to assess the influence of cardiac resynchronization therapy(CRT) on a series of humoral parameters crucial for the pathophysiology of chronic heart failure such as aldosterone or the inflammatory markers. Thirty eight consecutive patients (aged 66.3 +/- 9.6 years, 31 men - 82% ) with chronic heart failure (57.9% with ischaemic background and 42.1% of non-ischaemic etiology) in stable for at least 3 months, NYHA class III - IV despite optimized pharmacotherapy, with left ventricular ejection fraction (LVEF)or = 35% and wide QRS complex (or = 120 ms) had the blood serum tested for the concentrations of interleukin-6 (IL-6), interleukin-18 (IL-18), C-reactive protein (CRP) and aldosterone before and 12-16 weeks after CRT introduction. In the study group aldosterone concentrations were significantly reduced. Among the inflammatory markers the level of IL-6 decreased, IL-18 concentrations showed a falling trend (445.1 +/- 225.7 pg/ml vs 418.4 +/- 229.6 pg/ml, p = 0.052), whereas no change of CRP serum contain was noted. It was showed that cardiac resynchronization therapy had an impact on systemic inflammation and hormonal status in patients with chronic heart failure during short-term observation.
- Published
- 2011
26. Clinical and classic echocardiographic features of patients with, and without, left ventricle reverse remodeling following the introduction of cardiac resynchronization therapy
- Author
-
Jerzy, Wiliński, Danuta, Czarnecka, Wiktoria, Wojciechowska, Małgorzata, Kloch-Badełek, Marek, Jastrzębski, Bogumiła, Bacior, Tomasz, Sondej, Piotr, Kusak, Anna, Przybyła, and Kalina, Kawecka-Jaszcz
- Subjects
Male ,Ventricular Remodeling ,Myocardial Ischemia ,Middle Aged ,Prognosis ,Peptide Fragments ,Ventricular Function, Left ,Cardiac Resynchronization Therapy ,Logistic Models ,Echocardiography ,Predictive Value of Tests ,Atrial Fibrillation ,Multivariate Analysis ,Natriuretic Peptide, Brain ,Prevalence ,Humans ,Female ,Aged - Abstract
The aim of the study was to assess clinical and classic echocardiographic data in patients with different cardiac resynchronization therapy (CRT) outcomes.Sixty consecutive patients (aged 66.3 ± 8.7 years, 57 men) with chronic heart failure (CHF) in New York Heart Association (NYHA) classes III-IV despite optimized pharmacotherapy, with left ventricular end-diastolic diameter (LVEDD)55 mm, left ventricular ejection fraction £ 35% and wide QRS complex (≥ 120 ms), including individuals with permanent atrial fibrillation (AF) and single- and dual-chamber pacing, were assessed firstly before, and secondly three months after, biventricular heart stimulator implantation (excluding three patients who died during the follow-up). Patients developing ≥ 10% reduction of left ventricular end-systolic volume (LVESV) were classified as responders to CRT.The group of responders (n = 34, 59.7%) and the group of non-responders (n = 23, 40.3%) did not differ regarding baseline echocardiographic parameters or in terms of clinical data of age, gender, concomitant diseases, smoking or pharmacological treatment. The differences involved higher rates of ischemic CHF background, prevalence of hypertension and permanent AF, and a higher concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) among the non-responders. In the multivariate logistic regression analysis, NT-proBNP, body mass index (BMI) and the presence of permanent AF correlated negatively with the magnitude of LVESV reduction following CRT introduction.Classic echocardiographic data did not predict left ventricle reverse remodeling. Higher rates of ischemic CHF aetiology, hypertension, permanent AF and higher NT-proBNP concentration were found in the group without at least 10% LVESV reduction at the three month follow-up. NT-proBNP, BMI and the presence of permanent AF had negative effects on the magnitude of LVESV.
- Published
- 2011
27. Thermodynamic and acoustic properties of mixtures of dibromomethane + heptane
- Author
-
Anna Przybyła, Mirosław Chorążewski, Wojciech Marczak, and Edward Zorębski
- Subjects
Heptane ,Materials science ,Isentropic process ,Intermolecular force ,Binary mixtures ,Thermodynamics ,Mole fraction ,Condensed Matter Physics ,Dibromomethane ,chemistry.chemical_compound ,chemistry ,Volume (thermodynamics) ,Speed of sound ,Isobaric process - Abstract
Densities and speeds of ultrasound in binary mixtures of dibromomethane with heptane have been measured within the temperature range from 288.15 K to 318.15 K. From the experimental data, the thermodynamic excess volume, molar isobaric expansion, molar isentropic compression, and ultrasonic speed were calculated. The excess volume and excess isentropic compression have opposite signs, whereas the excess isobaric expansion is an S-shaped function of the mole fraction. An explanation was suggested to account for the excesses in terms of intermolecular interactions. It involved energetic and steric factors. Moreover, it was shown that the positive excess sound speed results almost entirely from the negative excess compression.
- Published
- 2011
28. [Natural interferon alpha (Le-IFNalpha) treatment in patients with thrombocytopenia during chronic HCV infection--our observations]
- Author
-
Joanna, Krzowska-Firych, Anna, Przybyła, and Roma, Modrzewska
- Subjects
Adult ,Male ,Adolescent ,Remission Induction ,Humans ,Interferon-alpha ,Female ,Hepatitis C, Chronic ,Middle Aged ,Antiviral Agents ,Thrombocytopenia ,Aged - Abstract
The aim of our study was to assess efficacy and safety of antiviral treatment with natural interferon alpha in patients with thrombocytopenia during chronic HCV infection. The study group consisted of 14 patients infected with HCV genotype lb. There were 8 women and 6 men (mean age 50). 11 of these had compensated liver cirrhosis. Three patients had previous reIFN or PegIFN alpha therapy with severe adverse events and lack of sustained viral response (SVR). Sustained viral response was achieved in 4 patients. Only in one case therapy was discontinued due to symptomatic hemorrhagic purpura.
- Published
- 2009
29. Serum zinc (Zn) level dynamics in blood serum of patients with acute viral hepatitis B and early recovery period
- Author
-
Hanna, Fota-Markowska, Anna, Przybyła, Irena, Borowicz, and Roma, Modrzewska
- Subjects
Adult ,Zinc ,Adolescent ,Reference Values ,Acute Disease ,Disease Progression ,Humans ,Reproducibility of Results ,Recovery of Function ,Middle Aged ,Hepatitis B ,Sensitivity and Specificity ,Aged - Abstract
The aim of the present study was an analysis of serum zinc level dynamics in patients with acute hepatitis B and early recovery period compared with control group. The investigation included 39 patients aged 18-76 hospitalised in the Department of Infectious Diseases of the Medical University of Lublin, because of acute hepatitis B. Determinations of zinc (Zn) level in blood serum were made four times during hospitalisation and once, four weeks after discharging from the clinic in the early recovery period using atomic absorption spectrometry (AAS). The control group included 24 persons aged 22-69. Zinc (Zn) levels of those people were determined once. The obtained numerical data were subjected to statistical analysis. Lack of significant differences between men and women allowed to calculate the range of our norm, which was assumed at the level of M +/- 2SD, that is between 12.948-19.036 mumol/l. The significantly decreased serum zinc level was observed during hospitalisation while the differences stated in the serum level of this element in initial and early recovery determination compared with control group results are markedly at random.
- Published
- 2003
30. Prolactin concentration in the serum of male patients with chronic hepatitis C
- Author
-
Sławomir, Kiciak, Hanna, Fota-Markowska, Irena, Borowicz, Roma, Modrzewska, and Anna, Przybyła
- Subjects
Adult ,Male ,Reference Values ,Statistics as Topic ,Humans ,Hepatitis C, Chronic ,Prolactin - Abstract
In this work we analysed the dynamics of prolactin serum concentration in male patients with chronic hepatitis C. A group of 52 men were included in the study, 26 of them constituted the control group. The diagnosis of the disease was confirmed by the presence of HCV-RNA in the serum and by the histological examination of the liver. None of the examined men was diagnosed with any co-existing disease nor any infection markers of HAV and HBV were found. The prolactin concentration was determined in the serum of patients twice: on the 2nd day of hospitalisation and after 4 weeks of hospitalisation by the use of radioimmunological method (RIA) applying a prepared set of reagents RIA-PROL-CTK-4 (Sorin Biomedica, Italy). The results were statistically analysed. An analysis of the dynamics of prolactin serum concentration in male patients with chronic hepatitis C shows a statistically important increase in this hormone serum concentration.
- Published
- 2003
31. Water-induced aggregation and hydrophobic hydration in aqueous solutions of N-methylpiperidine
- Author
-
Michał Zorębski, Wojciech Marczak, Piotr Lodowski, Dorota Truszkowska, Marta Łężniak, Anna Przybyła, and László Almásy
- Subjects
Aqueous solution ,Spinodal decomposition ,General Chemical Engineering ,Clathrate hydrate ,02 engineering and technology ,General Chemistry ,Neutron scattering ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Mole fraction ,01 natural sciences ,Lower critical solution temperature ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Pyridine ,Molecule ,Physical chemistry ,Organic chemistry ,0210 nano-technology - Abstract
Liquid system N-methylpiperidine–water shows a miscibility gap with a lower critical solution temperature of 316.7 K. The phase separation is most likely due to the aggregation of N-methylpiperidine–water complexes, evident in the intensity of the small-angle neutron scattering at temperatures much lower than the LCST. Such complexes arise because the attraction forces between unlike molecules are stronger than the water–water ones, and aggregation is possible through the O–H⋯O bonds involving the hydration water molecules. The aggregates are dynamic structures with nanoseconds-order relaxation times, as it was estimated by the ultrasonic absorption experiment. While hydrophilic aggregation prevails at relatively high concentrations of the amine, the hydrophobic hydration is possible at low concentrations, likely consisting of the formation of structures resembling those in the sH clathrates observed in the solid state. The hydrophobic hydration of N-methylpiperidine is manifested in the minima of the partial volume isotherms at the amine mole fraction close to 0.01 and in the limiting partial molar compression approximately equal to zero. Essential similarity of the N-methylpiperidine–water system to aqueous solutions of pyridine and its methyl derivatives studied previously, suggests that those amines are potential clathrate hydrate promoters.
- Published
- 2013
- Full Text
- View/download PDF
32. P8.9 EFFECT OF CARDIAC RESYNCHRONISATION THERAPY ON THE ARTERIAL STIFFNESS
- Author
-
Anna Przybyla and Danuta Czarnecka
- Subjects
Specialties of internal medicine ,RC581-951 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Development of cardiac resynchronisation therapy (CRT) in recent years became a breakthrough in treatment of severe heart failure, as it improves exercise capacity, reduces a rate of hospitalisations due to heart failure exacerbation, and the mortality rate, as well as improves quality of patients’ life. However, data on CRT effects on a number of heart failure comorbidities remains scarce. The aim of this study was evaluation of CRT effect on the arterial stiffness. Methods: The study covered a group of 55 patients (45 men and 10 women; mean age 67.04 ± 9.13 years) with chronic heart failure stable for at least last 3 months, in the NYHA functional class III or IV despite optimal pharmacotherapy, with a reduced left ventricular ejection fraction (LVEF) ≤ 35%, wide QRS complexes ≥ 120 ms. Before the resynchronisation system was implanted and after twelve months of observation arterial stiffness was evaluated with the carotid-femoral pulse wave velocity (PWV). Results: Statistically significant changes weren’t demonstrated for carotid-femoral pulse wave velocity value, only a tendency for its reduction (11,73 ± 2,37 m/s vs 11,32 ± 2,78 m/s, p = 0,08). Conclusions: After the resynchronisation system implantation, no statistically significant change in arterial stiffness was observed, only a trend towards its reduction.
- Published
- 2015
- Full Text
- View/download PDF
33. P8.11 EFFECT OF CARDIAC RESYNCHRONISATION THERAPY ON THE AUTONOMIC NERVOUS SYSTEM FUNCTION
- Author
-
Anna Przybyla and Danuta Czarnecka
- Subjects
Specialties of internal medicine ,RC581-951 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Development of cardiac resynchronisation therapy (CRT) in recent years became a breakthrough in treatment of severe heart failure. The aim of this study was evaluation of CRT effect on the autonomous nervous system function. Methods: The study covered a group of 55 patients (45 men, 10 women; mean age 67.04±9.13 years) with chronic heart failure stable for at least last 3 months, in the NYHA functional class III or IV despite optimal pharmacotherapy, with a reduced left ventricular ejection fraction ≤ 35%, wide QRS complexes ≥ 120 ms, and sinus rhythm present during the examination. Before the resynchronisation system was implanted and after three months of observation arterial baroreflex sensitivity (BRS) was evaluated with the sequence technique, and with the α coefficient and the transfer function. Results: Three months after implantation of the CRT device, a statistically significant increase in the arterial baroreflex sensitivity was observed for all methods used in the study, both when lying and breathing spontaneously (BRSseq: 5,96±2,07 ms/mmHg vs 7,64±4,73 ms/mmHg, p
- Published
- 2015
- Full Text
- View/download PDF
34. A Positive Control for Detection of Functional CD4 T Cells in PBMC: The CPI Pool
- Author
-
Annemarie Schiller, Ting Zhang, Ruliang Li, Andrea Duechting, Srividya Sundararaman, Anna Przybyla, Stefanie Kuerten, and Paul V. Lehmann
- Subjects
PBMC quality assessment ,PBMC cryopreservation ,CD4 cell function ,ELISPOT ,ImmunoSpot ,immune monitoring ,Cytology ,QH573-671 - Abstract
Testing of peripheral blood mononuclear cells (PBMC) for immune monitoring purposes requires verification of their functionality. This is of particular concern when the PBMC have been shipped or stored for prolonged periods of time. While the CEF (Cytomegalo-, Epstein-Barr and Flu-virus) peptide pool has become the gold standard for testing CD8 cell functionality, a positive control for CD4 cells is so far lacking. The latter ideally consists of proteins so as to control for the functionality of the antigen processing and presentation compartments, as well. Aiming to generate a positive control for CD4 cells, we first selected 12 protein antigens from infectious/environmental organisms that are ubiquitous: Varicella, Influenza, Parainfluenza, Mumps, Cytomegalovirus, Streptococcus, Mycoplasma, Lactobacillus, Neisseria, Candida, Rubella, and Measles. Of these antigens, three were found to elicited interferon (IFN)-γ-producing CD4 cells in the majority of human test subjects: inactivated cytomegalo-, parainfluenza-, and influenza virions (CPI). While individually none of these three antigens triggered a recall response in all donors, the pool of the three (the ‘CPI pool’), did. One hundred percent of 245 human donors tested were found to be CPI positive, including Caucasians, Asians, and African-Americans. Therefore, the CPI pool appears to be suitable to serve as universal positive control for verifying the functionality of CD4 and of antigen presenting cells.
- Published
- 2017
- Full Text
- View/download PDF
35. Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells
- Author
-
Andrea Duechting, Anna Przybyla, Stefanie Kuerten, and Paul V. Lehmann
- Subjects
cytokine kinetics ,ELISPOT ,CD4 cells ,T cells ,immune monitoring ,multiplexing ,Cytology ,QH573-671 - Abstract
During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively. Traditionally, these cytokines are measured within 6 h in flow cytometry. We show here that 6 h of stimulation is sufficient to detect peptide-induced production of IFN-γ, but 24 h are required to reveal the full frequency of protein antigen-specific Th1 cells. Also the detection of IL-2 producing Th1 cells requires 24 h stimulation cultures. Measurements of IL-4 producing Th2 cells requires 48-h cultures and 96 h are required for frequency measurements of IL-5 and IL-17 secreting T cells. Therefore, accounting for the differential secretion kinetics of these cytokines is critical for the accurate determination of the frequencies and ratios of antigen-specific Th1, Th2, and Th17 cells.
- Published
- 2017
- Full Text
- View/download PDF
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