| 1. |
- Booy, Evan P., et al.
(författare)
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Monoclonal and bispecific antibodies as novel therapeutics
- 2006
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Ingår i: Archivum Immunologiae et Therapiae Experimentalis. - : Birkhäuser-Verlag. - 0004-069X .- 1661-4917. ; 54:2, s. 85-101
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Tidskriftsartikel (refereegranskat)abstract
- Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been implicated in many human cancers and is associated with poor prognosis. Tumor growth has been shown to be decreased by interrupting this process of extensive growth factor-mediated signaling by directly targeting either the surface receptor or the ligand and thereby preventing cell survival and promoting apoptosis. Monoclonal antibodies have long been eyed as a potential new class of therapeutics targeting cancer and other diseases. Antibody-based therapy initially entered clinical practice when trastuzumab/Herceptin became the first clinically approved drug against an oncogene product as a well-established blocking reagent for tumors with hyperactivity of epidermal growth factor signaling pathways. In the first part of this review we explain basic terms related to the development of antibody-based drugs, give a brief historic perspective of the field, and also touch on topics such as the "humanization of antibodies" or creation of hybrid antibodies. The second part of the review gives an overview of the clinical usage of bispecific antibodies and antibodies "armed" with cytotoxic agents or enzymes. Further within this section, cancer-specific, site-specific, or signaling pathway-specific therapies are discussed in detail. Among other antibody-based therapeutic products, we discuss: Avastin (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX-210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000), Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of the review deliberates upon potential problems associated with cancer immunotherapy.
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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. |
- Maddika, Subbareddy, et al.
(författare)
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Cancer-specific toxicity of apoptin is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a Nur77-dependent pathway
- 2005
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Ingår i: Journal of Cell Science. - : The Company of Biologists Ltd.. - 0021-9533 .- 1477-9137. ; 118, s. 4485-4493
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Tidskriftsartikel (refereegranskat)abstract
- Apoptin, a small proline-rich protein derived from the chicken anaemia virus, induces cell death selectively in cancer cells. The signalling pathways of apoptin-induced, cancer cell-selective apoptosis are not well understood. Here, we demonstrate that apoptin triggers apoptosis by activating the mitochondrial/intrinsic pathway, and that it acts independently of the death receptor/extrinsic pathway. Jurkat cells deficient in either FADD or caspase-8 (which are both necessary for the extrinsic pathway) were equally as sensitive to apoptin as their parental clones. This demonstrates that apoptin is likely to act through the mitochondrial death pathway. Apoptin treatment causes a loss of mitochondrial membrane potential, and release of the mitochondrial proteins cytochrome c and apoptosis-inducing factor. Apoptin-induced cell death is counteracted by the anti-apoptotic Bcl-2 family members, Bcl-2 itself and Bcl-XL, as shown in Jurkat leukaemia cells. In addition, we describe the processing and activation of caspase-3. By contrast, cleavage of caspase-8, which is predominantly triggered by the death receptor pathway, is not observed. Furthermore, apoptin triggers the cytoplasmic translocation of Nur77, and the inhibition of Nur77 expression by siRNA significantly protects MCF7 cells from apoptin-triggered cell death. Thus, our data indicate that the apoptin death signal(s) ultimately converges at the mitochondria, and that it acts independently of the death receptor pathway.
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