| 1. |
- Dumanski, Jan P., et al.
(author)
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Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
- 2021
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 78:8, s. 4019-4033
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Journal article (peer-reviewed)abstract
- Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.
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| 2. |
- Kroczak, Tadeusz J., et al.
(author)
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The emerging importance of DNA mapping and other comprehensive screening techniques, as tools to identify new drug targets and as a means of (cancer) therapy personalisation
- 2006
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In: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1472-8222 .- 1744-7631. ; 10:2, s. 289-302
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Journal article (peer-reviewed)abstract
- Every human being is genetically unique and this individuality is not only marked by morphologic and physical characteristics but also by an individual's response to a particular drug. Single nucleotide polymorphisms (SNPs) are largely responsible for one's individuality. A drug may be ineffective in one patient, whereas the exact same drug may cure another patient. Recent advances in DNA mapping and other screening technologies have provided researchers and drug developers with crucial information needed to create drugs that are specific for a given individual. In the future, physicians will be able to prescribe individualised drugs adjusted to, for example, activities of specific enzymatic pathways that would either be targeted by these drugs, or would be responsible for drug conversion or inactivation. Furthermore, the mapping of the human genome allows broader development and application of drugs that act on the level of gene transcription rather than as simple biochemical inhibitors or activators of certain enzymes. Such new approaches will maximise desired therapeutic results and may completely eliminate severe side effects. To illustrate the potential of genetic translational research, the authors discuss available analytical methodologies such as; gene arrays, flow cytometry-based screening for SNPs, proteomics, metabolomics, real-time PCR, and other methods capable of detecting both SNPs, as well as more profound changes in cell metabolism. Finally, the authors provide several examples that focus mostly on targeting protein-DNA interactions, but also other processes.
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| 3. |
- Sieminska, Izabela, et al.
(author)
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The Level Of Myeloid Derived-Suppressor Cells In Peripheral Blood Of Patients With Prostate Cancer After Various Types Of Therapy
- 2020
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In: Polish Journal of Pathology. - 1233-9687 .- 2084-9869. ; 71:1, s. 46-54
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Journal article (peer-reviewed)abstract
- Prostate cancer is one of the most frequent cancers in men. Although several treatment options exist, their clinical effectiveness is still not satisfactory. One the possible reason of such situation might be the presence of myeloid-derived suppressor cells (MDSC) and their pro-turnorigenic activity. MDSC possess irnmunosuppressive ability and in many studies were shown to support tumor development and progression. In this study we addressed the question whether commonly used therapies of prostate cancer affect the level of MDSC populations in the patients' blood. We compared the level of granulocytic (Gr-MDSC), monocytic (Mo-MDSC) and early stage MDSC (eMDSC) in the blood of patients at different clinical stage and different tumor grading scores, who underwent either surgery or hormonal therapy alone or were given a combined treatment, including e.g. radiotherapy. The obtained results showed that the level of Gr-MDSC was significantly lower in all treated patients comparing to untreated group. On the other hand, surgery or hormonal therapy alone did not affect the level of Mo-MDSC. These results were independent of the PSA level, the tumor grading and clinical stage of the patients. In conclusion, we suggest that Mo-MDSC should be considered as a potential therapy target in the course of prostate cancer treatment to enhance its anti-tumor effectiveness.
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