| 1. |
- Ghavami, Saeid, et al.
(författare)
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Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway
- 2008
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Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley-Blackwell. - 1582-1838 .- 1582-4934. ; 12:3, s. 1005-1022
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Tidskriftsartikel (refereegranskat)abstract
- Brevinin-2R is a novel non-hemolytic defensin that was isolated from the skin of the frog Rana ridibunda. It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T-cell leukemia), BJAB (B-cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF-7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells including peripheral blood mononuclear cells (PBMC), T cells and human lung fibroblasts. Jurkat and MCF-7 cells overexpressing Bcl2, and L929 and MCF-7 over-expressing a dominant-negative mutant of a pro-apoptotic BNIP3 (ΔTM-BNIP3) were largely resistant towards Brevinin-2R treatment. The decrease in mitochondrial membrane potential (ΔΨm), or total cellular ATP levels, and increased reactive oxygen species (ROS) production, but not caspase activation or the release of apoptosis-inducing factor (AIF) or endonuclease G (Endo G), were early indicators of Brevinin-2R-triggered death. Brevinin-2R interacts with both early and late endosomes. Lysosomal membrane permeabilization inhibitors and inhibitors of cathepsin-B and cathepsin-L prevented Brevinin-2R-induced cell death. Autophagosomes have been detected upon Brevinin-2R treatment. Our results show that Brevinin-2R activates the lysosomalmitochondrial death pathway, and involves autophagy-like cell death.
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| 2. |
- Johar, Dina, et al.
(författare)
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Inflammatory response, reactive oxygen species, programmed (necrotic-like and apoptotic) cell death and cancer
- 2004
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Ingår i: Roczniki Akademii Medycznej w Bialymstoku (1995). ; 49, s. 31-39
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Forskningsöversikt (refereegranskat)abstract
- In this short review we attempt to establish and/or strengthen connections between clinical, inflammatory manifestation of cancer, inflammatory processes driven by lipoxy-metabolites and their contribution to immortalized phenotype and apoptosis inhibition. Particularly the resemblance between symptoms of inflammation and signs associated with cancer chemotherapy and/or cytokine therapy is illustrated. In this context the role of apoptosis and necrosis in inflammation as well as the role of RedOx processes and lipid-oxidizing enzymes particularly cyclooxygenase-2 (COX-2) and also to lesser extend the 5-lipooxygenase (5-LOX) is highlighted. The multitude of biological effects of reactive oxygen species is shortly summarized and some aspects of it are being discussed in greater detail. Apoptotic cell death is discussed in the context of the "resolve-phase" of an inflammatory response. The disturbance of apoptosis is mainly deliberated in the framework of insufficient removal of immuno-effector cells that may cause autoimmunity. The role of COX-2 in apoptosis resistance is being highlighted mainly in the context of malignant transformation. The mechanism of cell death (apoptotic or necrotic) and its influence on the immune system and potential benefits of necrotic cell death induction during cancer chemotherapy is indicated.
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| 3. |
- Kroczak, Tadeusz J., et al.
(författare)
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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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Ingår i: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1472-8222 .- 1744-7631. ; 10:2, s. 289-302
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Tidskriftsartikel (refereegranskat)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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