| 1. |
- Lindmark, G, et al.
(författare)
-
Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer : relation to survival.
- 1993
-
Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 19:1, s. 50-60
-
Tidskriftsartikel (refereegranskat)abstract
- The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA-ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator.
|
|
| 2. |
- Lindmark, G, et al.
(författare)
-
Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer.
- 1993
-
Ingår i: Laboratory Investigation. - 0023-6837 .- 1530-0307. ; 69:6, s. 682-9
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear.EXPERIMENTAL DESIGN: The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively.RESULTS: All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive cells), whereas the nature of the remaining stromal cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The extent of clusters of PDGF beta-receptor expressing cells varied considerably between tumors, and its prognostic value was considered in the entire tumor material. The number of clusters did, however, not correlate to tumor differentiation, tumor stage according to Dukes', or outcome.CONCLUSIONS: The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.
|
|
| 3. |
- Sundín, Anders, et al.
(författare)
-
Radioimmunolocalization of hepatic metastases and subcutaneous xenografts from a human colonic cancer in the nude rat : Aspects of tumour implantation site and mode of antibody administration
- 1993
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 877-885
-
Tidskriftsartikel (refereegranskat)abstract
- Antibody localization was analyzed following intraperitoneal (i.p.) or intravenous (i.v.) injection of the 125I-labelled anti-CEA-MAb I-38S1 in 44 nude rats, in order to evaluate the influence of tumour implantation site and the route of MAb administration. The animals were xenografted with a human colonic cancer (LS 174 T), either in the form of hepatic metastases, subcutaneous (s.c.) tumours or both. Tissue measurements, 4 days after MAb injection, showed better uptake for hepatic than for s.c. tumours, irrespective of the route of antibody administration. Antibody accumulation per g liver metastases was not size dependent for noduli weighing between 4 and 1,110 mg. MAb excretion evaluated in 20 animals and blood activity studied in 11 rats were equivalent 24-96 h following i.p. and i.v. injection. Dissimilar autoradiographic patterns were seen in hepatic metastases with predominantly peripherally located clusters following i.p. and more homogeneously distributed grains after i.v. MAb administration. The results indicate that tumour implantation site has a quantitative, and the route of administration at least a qualitative impact on the tumour accretion of anti-CEA MAb I-38S1 in the present xenograft model.
|
|
