Changes in endogenous cytokines, adhesion molecules and platelets during cytokine-induced tumour necrosis
| Autor: | S. de Kossodo, C. Upton, Nick East, S. Gschmeissner, Robert B. Moore, Frances R. Balkwill |
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| Rok vydání: | 1995 |
| Předmět: |
Cancer Research
Pathology Necrosis medicine.medical_treatment Apoptosis Polymerase Chain Reaction Receptors Tumor Necrosis Factor Mice Tumor Cells Cultured Interferon gamma RNA Neoplasm Receptor biology Cell adhesion molecule Drug Synergism Adenocarcinoma Mucinous Recombinant Proteins Specific Pathogen-Free Organisms Gene Expression Regulation Neoplastic Chemotaxis Leukocyte Cytokine Oncology Connective Tissue Receptors Tumor Necrosis Factor Type I Cytokines Female Tumor necrosis factor alpha medicine.symptom Research Article medicine.drug medicine.medical_specialty Stromal cell Molecular Sequence Data Mice Nude Breast Neoplasms Hemorrhage Interferon-gamma Platelet Adhesiveness Antigens CD medicine Animals Humans Immunologic Factors Receptors Tumor Necrosis Factor Type II RNA Messenger Interleukin 6 Base Sequence Tumor Necrosis Factor-alpha Microcirculation Rats biology.protein Cancer research Endothelium Vascular Cell Adhesion Molecules Neoplasm Transplantation |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.1995.481 |
| Popis: | The aim of this study was to investigate mechanisms of anti-tumour activity and necrosis induced by combinations of tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). In a breast cancer xenograft model, locally injected recombinant human TNF-alpha arrested growth of established tumours in the absence of overt necrosis. Macroscopic necrosis occurred when rat IFN-gamma, which had no anti-tumour activity as a single agent, was given systemically. Treatment with TNF-alpha and IFN-gamma caused focal engorgement of tumour capillaries with erythrocytes, intravascular recruitment of polymorphonuclear cells and platelet adherence to the tumour vascular endothelium 4 h after the combined treatment. This was followed by destruction of tumour vascular endothelium and both necrosis and apoptosis of tumour cells. Concomitant with these changes, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the increase of stromal (murine) mRNA levels for TNF-alpha, TNF receptor 55 kDa, TNF receptor 75 kDa, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, P-selectin and interleukin 6 (IL-6). Thus, the effect of the combined TNF-alpha and IFN-gamma therapy involved the selective destruction of the tumour vasculature, death of tumour cells and increased expression of a series of stromal cytokines, cytokine receptors and adhesion molecules, which could be implicated in the observed events. Images Figure 3 Figure 4 Figure 5 |
| Databáze: | OpenAIRE |
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