| 1. |
- Graf, Wilhelm, et al.
(författare)
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Induction and quantification of hepatic metastases from a human colonic cancer in the nude rat
- 1992
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 18:6, s. 608-614
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Tidskriftsartikel (refereegranskat)abstract
- Nude rats were injected with human colonic cancer cells (LS 174 T) in the superior mesenteric vein and the extent of hepatic metastases at sacrifice was estimated by visual inspection and computer-based area calculation. After 3 weeks, 5.0 x 10(6) cells caused hepatic metastases in 14/14 rats whereas 0.5 x 10(6) cells failed to produce liver metastases in 4/4 rats (P < 0.001). Injection of 1.0 x 10(7) cells caused portal vein occlusion in 3/5 rats. Extrahepatic tumour growth was rare; lung metastases were observed in four rats, and three rats had local tumour in the abdomen. The average extent of hepatic tumour replacement was 20.2 +/- 4.0%. Injection of embolies or single cells did not affect the incidence or extent of hepatic metastases. The incidence of hepatic metastases was similar in male and female rats, but the extent of hepatic tumour was larger in males (24.6%) than in females (3.2%) (P = 0.005). The pathophysiological similarities to human disease should make this model suitable for diagnostic and therapeutic studies with clinical application.
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| 2. |
- Graf, W, et al.
(författare)
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The influence of early postoperative intraperitoneal chemotherapy on human wound healing.
- 1994
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 57:3, s. 394-400
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Tidskriftsartikel (refereegranskat)abstract
- Cell ingrowth, hydroxyproline accumulation, and mRNA expression of collagen I were measured in two polytetrafluoroethylene grafts implanted subcutaneously at the time of colorectal cancer surgery to evaluate the influence of early postoperative chemotherapy on human wound healing. Eleven patients treated with intraperitoneal 5-fluorouracil and intravenous folinic acid Days 1-6 after operation were compared with 15 patients who underwent surgery alone. At 1 week, chemotherapy-treated patients had accumulated less hydroxyproline (mean 0.35 +/- 0.33 micrograms/cm) compared with untreated patients (mean 0.73 +/- 0.37 micrograms/cm, P < 0.05). By 2 weeks, the hydroxyproline content had increased sixfold in the chemotherapy group (P < 0.01) and threefold in the nonchemotherapy group (P < 0.01) and there was no difference between the groups. Cell and connective tissue ingrowth and total RNA content did not differ between the groups at any point in time, but at 1 week the mRNA expression of collagen I was higher in the chemotherapy group (P < 0.05). These results indicate that collagen accumulation in human subjects is reduced during a short course of postoperative chemotherapy and normalizes after the end of treatment.
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| 3. |
- Lampic, Claudia, et al.
(författare)
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Coping, psychosocial well-being and anxiety in cancer patients at follow-up visits
- 1994
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 33:8, s. 887-894
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Tidskriftsartikel (refereegranskat)abstract
- Coping, psychosocial well-being, situation-specific anxiety and cancer-related worry were assessed in 197 consecutive cancer patients attending follow-up visits. Participants completed questionnaire on three occasions: at the follow-up visit, some days later (n = 175) and three weeks later (n = 125). High levels of coping styles 'Anxious Preoccupation' and 'Helplessness/Hopelessness' were associated with low levels of psychosocial well-being, more situation-specific anxiety and more cancer-related worry. High levels of 'Fighting Spirit' and 'Fatalistic' were found to be associated with high psychosocial well-being and, for 'Fighting Spirit', also with less cancer-related worry. Patients with a 'dismal' prognosis were found to have higher levels of 'Helplessness/Hopelessness' than patients with a more 'favorable' prognosis. Clinical implications of these findings are discussed.
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| 4. |
- Lindmark, G, et al.
(författare)
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Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer : relation to survival.
- 1993
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 19:1, s. 50-60
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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.
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| 5. |
- Lindmark, G, et al.
(författare)
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Prognostic predictors in colorectal cancer.
- 1994
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Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 37:12, s. 1219-27
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Better prognostic predictors in colorectal cancer than the Dukes stage are necessary for individualized therapy and follow-up.METHODS: Survival among 212 patients operated on for colorectal cancer was examined regarding various clinical, histopathologic, cellular, and serologic tumor characteristics.RESULTS: Beside the Dukes stage, which was the most powerful variable, the erythrocyte sedimentation rate, leukocyte blood count, alkaline phosphatase, aspartate aminotransferase, six different serum tumor markers, number of small blood vessels, and age were found to be significantly associated with survival. The leukocyte blood count, alkaline phosphatase, and aspartate aminotransferase retained their significance in a multivariate model including tumor differentiation, local tumor stage, and age. Inclusion of tissue polypeptide antigen, the most powerful tumor marker in the multivariate model, showed that only the tumor stage, tissue polypeptide antigen, and age were statistically significantly correlated to survival. This was valid both for the group of patients considered as potentially curable and for those who potentially have been cured (Dukes Stages A-C).CONCLUSIONS: A great number of prognostic predictors failed to discard Dukes stage as the best one. One serum tumor marker, tissue polypeptide antigen, contains independent additional prognostic information.
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| 6. |
- Lindmark, G, et al.
(författare)
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Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer.
- 1993
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Ingår i: Laboratory Investigation. - 0023-6837 .- 1530-0307. ; 69:6, s. 682-9
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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.
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| 7. |
- Sundín, Anders, et al.
(författare)
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Contrast-enhanced CT scanning in vivo for the quantification of hepatic metastases from a human colonic cancer in the nude rat
- 1992
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 18:6, s. 615-623
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic metastases were induced in nude rats by intraportal injection of 2.5-5.0 x 10(6) cells from the human colonic cancer cell line LS 174 T. Quantification of tumour burden, expressed as relative metastatic area, was performed by contrast-enhanced computed tomography (CT) scanning in vivo (n = 14), contrast enhanced CT scanning post mortem (n = 21) and computer-based area calculation (CBAC) (n = 21). To determine the false-positive contribution to the estimated tumour burden by the evaluation procedures themselves, six rats without metastases were assessed. The quantification in the three different assessment groups was in close accordance in animals with an intermediate or extensive metastatic burden, but not in rats with a minor (< 4%) tumour burden. The results indicate that contrast-enhanced CT scanning can be used in this model to quantify hepatic metastases, except in animals with few and small lesions. Furthermore, the results suggest a potential for the assessment of therapeutic response by repeated contrast-enhanced CT scanning in vivo, as well as prospects for a corresponding evaluation in man.
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| 8. |
- Sundín, Anders, et al.
(författare)
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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
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 877-885
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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.
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