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F T Bosman

Publications and source records attributed to F T Bosman.

At least 109 records · Page 6Linked to original sources
PubMed1993

Endocrine cells in colorectal adenocarcinomas: incidence, hormone profile and prognostic relevance.

The occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial-cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA-positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA-positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon-like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA-positive tumors tended to be more aggressive than CGA-negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar-cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin-producing tumors showed intermediate behavior.

Adenocarcinoma↗
PubMed1993

Image cytometric DNA analysis in transitional cell carcinoma of the bladder.

BACKGROUND: The current study was initiated to investigate measurable objective and reproducible characteristics that might have prognostic significance in bladder cancer. METHODS: Tumor samples from 91 patients with primary transitional cell carcinoma (TCC) of the urinary bladder were studied by DNA image cytometry and cytogenetic analysis. Image cytometry is a more sensitive method of determining ploidy than flow cytometry, especially in tumors with a low number of aneuploid cells. RESULTS: There was a significant difference in survival between DNA image cytometry-determined diploid and nondiploid cases. The presence of nuclei with a high DNA content indicated poor prognosis. The 2C deviation index (2CDI) also was an indicator of survival. Image cytometry-determined factors also were found to be strong predictors of progression-free survival. In multivariate analysis, 2CDI was the only cytometric parameter with an independent but weak correlation with survival. In multivariate analysis, none of the cytometric parameters had an important contribution to prediction of progression-free survival. In superficial tumors (Ta and T1), 2CDI appeared to be the most important independent predictor of survival. With respect to progression-free survival, tumors with a high mitotic index proved to have a worse prognosis. CONCLUSIONS: Parameters determined by DNA image cytometry appear to be valuable in predicting survival and progression-free survival and may be useful in addition to the classic parameters of stage and grade, especially in superficial TCC.

Adult↗
PubMed1993

Patterns and composition of basement membranes in colon adenomas and adenocarcinomas.

We studied the distribution of type IV collagen and type VII collagen in the basement membranes of normal mucosa of the colon, adenomas, and adenocarcinomas using immunoperoxidase and immunofluorescence techniques. In normal mucosa, we found regular type IV collagen-positive basement membranes, lining vascular structures and mucosal epithelia. These basement membranes, however, lacked type VII collagen. In adenomas of the colon, intact basement membranes were observed through type IV collagen staining. Type VII collagen staining was also detected, but only in connection with dysplastic epithelium. Adjacent to the dysplastic epithelium in adenomas, histologically normal epithelium also showed type VII collagen staining along the basement membrane, but this was restricted to the epithelium of the luminal surface. These areas were also investigated for expression of keratins 8, 18, and 19, and keratins 5 and 8 (monoclonal antibodies NCL-5D3 and RCK 102, respectively), but altered differentiation was not detected using this technique. In adenocarcinomas of the colon, type IV collagen was irregularly deposited in the basement membrane of neoplastic tubules. Type VII collagen staining was detected only in well or moderately differentiated carcinomas and in higher amounts. Our findings therefore reveal a transient expression of type VII collagen in the transition of dysplastic epithelium into carcinoma, suggesting the involvement of type VII collagen in the process of early invasion.

Adenocarcinoma↗
PubMed1993

Identification of numerical chromosome aberrations in archival tumours by in situ hybridization to routine paraffin sections: evaluation of 23 phaeochromocytomas.

We have applied non-isotopic in situ hybridization (ISH) to interphase cell nuclei of 23 phaeochromocytomas (18 primary and 5 metastatic tumours) within routine paraffin-embedded tissue sections. Each tumour was screened for numerical aberrations with a defined alphoid repetitive DNA probe set containing DNA probes specific for chromosomes 1, 7, 15, and Y. Normal adrenal medullas and other normal human cell types served as cytogenetic controls. Preservation of tissue morphology enabled targeted analysis of tumour cells. The presence of numerical chromosome changes in the tumour cells could easily be evaluated by comparing the ISH results of the DNA probes. Numerical abnormalities not previously reported in this neoplasm included overrepresentation of chromosomes 1 and 7, loss of chromosome 15, and both gain and loss of chromosome Y (P values < 0.01). The percentage of aneuploid cell nuclei in a tumour correlated well with the percentage of cells in the 4C peak of flow cytometric DNA histograms from these neoplasms. We conclude that interphase ISH can be used for the identification of new and reported cytogenetic changes in tumour cell nuclei within archival tissue sections. This novel procedure also allows for retrospective analysis of previously not karyotyped material.

Adrenal Gland Neoplasms↗
PubMed1993

Integrins: cell adhesives and modulators of cell function.

Integrins encompass a family of cell-surface molecules which play a crucial role in cell-cell and cell-extracellular matrix interaction. Of these heterodimeric transmembrane glycoproteins (consisting of an alpha and beta chain) as yet at least 20 different types have been described, all with a different pattern of reactivity with extracellular matrix components. In this review the cell and tissue distribution of the integrins is discussed, with special emphasis on immunohistochemical localization of the beta 1 integrins and the alpha 6 beta 4 integrin. The beta 1 integrins comprise a subfamily in which eight alpha chains combine with one beta (the beta 1) chain. The alpha 2 beta 1, alpha 3 beta 1 and alpha 6 beta 1 and the alpha 6 beta 4 integrins are expressed on a wide variety of epithelia on the basolateral surface or exclusively on the basal surface facing the basement membrane (e.g. alpha 6 beta 1 and alpha 6 beta 4). Leucocyte integrins, which share a common beta 2 chain, occur almost exclusively on white blood cells and their precursors. The vitronectin receptors, which share a common alpha v chain, occur in a wide variety of cell types. Integrins play a major role in the interaction of the cell with the extracellular matrix in order to create and maintain tissue architecture. It has become clear, however, that through integrin-ligand interaction cell function is also modulated. Furthermore, in pathological conditions integrins play a role of some significance. Integrins mediate leucocyte traffic in developing inflammatory processes and function in neoplastic growth when it comes to invasion and metastasis.

Amino Acid Sequence↗
PubMed1993

Transfected c-Ha-ras oncogene enhances karyotypic instability and integrates predominantly in aberrant chromosomes.

A human colon tumor cell line, SW480, was transfected with the c-Ha-ras oncogene, the wild type c-Ha-ras gene, or the pSV2neo plasmid. Cytogenetic analysis and localization of chromosome integration sites were combined in an attempt to analyze the effects of transfection with the c-Ha-ras oncogene on the karyotype. All transfected cell lines showed new clonal chromosome abnormalities present in all cells, ranging from three new aberrations in pSV2neo-transfected SW480 cell lines to eight in c-Ha-ras oncogene-transfected SW480 cell lines. The level of expression of c-Ha-ras mRNA after transfection with the c-Ha-ras oncogene was positively correlated with increased genetic instability, reflected in enhanced karyotypic instability. A combination of banding and fluorescence in situ hybridization (FISH) was used to identify chromosome integration sites. Plasmids containing ras integrated predominantly in new structurally rearranged chromosomes (five of eight). Three of five integration sites in new structurally rearranged chromosomes were localized at or near translocation breakpoints situated in telomeric regions. Specific chromosomes were not involved in the chromosome rearrangements. The results indicate that 1) enhanced expression of c-Ha-ras mRNA correlates with an increase in genetic instability in c-Ha-ras oncogene-transfected SW480 cell lines, and 2) that no specific integration site was observed but ras-containing plasmids were located predominantly in aberrant chromosomes near or at translocation breakpoints involving telomeric bands.

Chromosome Aberrations↗
PubMed1993

Histology after stenting of human saphenous vein bypass grafts: observations from surgically excised grafts 3 to 320 days after stent implantation.

OBJECTIVES: To gain insight into the mechanism of stenting in humans and its short- and long-term implications, we studied the vascular wall of saphenous vein aortocoronary bypass grafts after implantation of the Wallstent. BACKGROUND: The implantation of a stent in aortocoronary bypass grafts may provide an alternative solution for revascularization in patients who are poor candidates for reoperation. Because human histopathologic findings after stenting with the Wallstent have not previously been described in detail, we examined graft segments that were surgically retrieved from 10 patients (21 stents) at 3 days to 10 months after implantation of the stent. METHODS: The grafts were examined by a combination of the following techniques: light microscopy, immunocytochemistry and both scanning and transmission electron microscopy. RESULTS: Early observations revealed that large amounts of platelets and leukocytes adhered to the stent wires during the first few days. At 3 months, the wires were embedded in a layered new intimal thickening, consisting of smooth muscle cells in a collagenous matrix. In addition, foam cells were abundant near the wires. Extracellular lipids and cholesterol crystals were found after 6 months. Smooth muscle cells and extracellular matrix formed the predominant component of restenosis. This new intimal thickening was lined with endothelium, in some cases showing defect intercellular junctions and abnormal adherence of leukocytes and platelets as late as 10 months after implantation. CONCLUSIONS: This type of stent is potentially thrombogenic and seems to be associated with extracellular lipid accumulation in venous aortocoronary bypass grafts.

Coronary Artery Bypass↗
PubMed1993

Quantitative and qualitative evaluation of renal injury induced by shock waves delivered with the Siemens C generator.

The tissue safety of a new shock wave generator, the Siemens C generator, was investigated in a porcine model. The tissue and functional effects of single treatments as well as retreatments were evaluated after 2 and 14 days. Quantitative morphologic and functional studies suggest that this device can be applied at its maximum energy up to 4000 shock waves (SW) without provoking damage that would lead to clinical concern. From this study, it appears justified to apply this device to patients suffering from stone disease to assess the clinical efficiency.

Animals↗
PubMed1993

Human Caco-2 cells transfected with c-Ha-Ras as a model for endocrine differentiation in the large intestine.

Endocrine cells occur in approximately 30% of all colorectal adenocarcinomas, and this feature appears to correlate with a relatively poor prognosis. To study the factors regulating endocrine differentiation in colorectal cancer, which may bear resemblance to the regulation of endocrine differentiation in normal intestinal mucosa, models in which differentiation can be manipulated are essential. However, endocrine features in colorectal cancer cell lines are scarce and are almost exclusively observed in xenografts, presumably as a result of differentiation induction by stromal components. We attempted to demonstrate endocrine differentiation in the colonic adenocarcinoma cell line Caco-2, which is frequently used as a model for enterocytic differentiation. In vitro endocrine tumor cells were not encountered. In vivo studies were cumbersome, because of the low take rate of Caco-2 cells. We did manage to establish nude mouse xenografts of Caco-2 cells by inoculating cells in collagen gel and by suppressing natural killer cell activity. In an attempt to induce a better take rate and to investigate the effect of Ras oncoprotein overexpression on endocrine differentiation, Caco-2 cells were transfected with a point-mutated c-Ha-Ras gene. The cell line Caco-2 EJ6, generated from these experiments, could be xenografted in nude mice with a high take rate, yielding a moderately well differentiated adenocarcinoma, morphologically identical to the tumors derived from untransfected Caco-2 cells. The xenografts displayed goblet cell, enterocytic, Paneth cell and endocrine differentiation. In vitro endocrine differentiation was observed neither under standard conditions nor with extracellular matrix components as differentiation inducers. We conclude that the Caco-2 cell line and its c-Ha-Ras transfected subline Caco-2 EJ6 in vivo display endocrine differentiation. Ras overexpression does not enhance endocrine differentiation. Due to its favorable growth properties in vivo, Caco-2 EJ6 is a suitable model for studies on endocrine differentiation in colorectal cancer.

Animals↗
PubMed1993

Cytogenetic analysis in transitional cell carcinoma of the bladder.

The potential use of numerical chromosomal abnormalities as predictive factors for the clinical behaviour of transitional cell carcinoma (TCC) was investigated. The effects on survival and progression-free survival were measured in 91 patients with TCC treated by transurethral resection. The survival rate of patients having tumours with a diploid chromosomal modal number was significantly better than that of patients having tumours with a hyperdiploid chromosomal modal number. The survival rate of patients having TCC with diploid cells only was also significantly better than that of patients having TCC with both diploid and hyperdiploid cells. Progression-free survival was significantly higher in patients having TCC with a diploid modal number of chromosomes than in patients with a hyperdiploid modal number. Simultaneous evaluation of the modal chromosome number or chromosomal range, histological grade, category and mitotic index of the tumour, and the patient's age and sex as prognostic factors in multivariate analyses showed that the category of bladder carcinomas was the most important factor in predicting the survival rate. In patients with superficial tumours (category Ta and T1) the modal chromosome number was the most important factor in predicting survival. For progression-free survival, the modal chromosome number appeared to be the most important factor. It was concluded that the modal chromosome number in TCC was useful in predicting survival in patients with superficial tumours and in predicting progression-free survival in patients with tumours of all categories.

Adult↗
PubMed1993

Extracellular matrix components induce endocrine differentiation in vitro in NCI-H716 cells.

Endocrine cells occur in +/- 30% of colorectal adenocarcinomas. The significance of this phenomenon in terms of tumor behavior is still controversial. Endocrine differentiation in colorectal cancer cell lines is almost confined to tumor xenografts in vivo, suggesting that endocrine differentiation might be regulated by epithelial-stromal interactions. This hypothesis was studied in the cecal adenocarcinoma-derived cell line NCI-H716 by comparing the expression of chromogranin A protein and messenger RNA in vivo and in vitro and by attempts to induce differentiation in vitro. We found that chromogranin A expression, which was strongest in vivo, could be significantly enhanced in vitro by culturing tumor cells in the presence of native extracellular matrix, on fibroblast feeder layers, and in a defined medium with basic fibroblast growth factor. The results suggest that the extracellular matrix induces endocrine differentiation through factors (e.g., basic fibroblast-growth factor) that may be produced by stromal cells and after secretion bind to the extracellular matrix.

Adenocarcinoma↗
PubMed1993

Epithelial-stromal interactions in colon cancer.

In this paper investigations concerning the interactions at the interface between tumor cells and tumor stroma are reviewed. As a model for tumor cell-extracellular matrix interaction human colorectal carcinoma cell lines, in vitro and in vivo, in nude mouse xenografts, were chosen. Based on the available data and on a review of the literature the following conclusions can be drawn. Most malignant epithelial neoplasms at the site of tumor cell invasion display defects in the epithelial basement membrane. This is not merely the result of enzymatic dissolution but rather reflects a shift in basement membrane turnover towards degradation. Elsewhere in the same primary tumor or in a metastasis the balance might be shifted more towards basement membrane deposition. The tendency of a tumor to deposit basement membranes reflects the biological potential of the neoplasm. Basement membranes are deposited by stromal cells or by a concerted action of tumor and stromal cells. Differentiation in a carcinoma is modulated by factors in the extracellular matrix. Endocrine differentiation can be induced in vitro by native basement membranes but also by direct contact of the tumor cells with fibroblasts. Basic FGF is one of the extracellular matrix factors with differentiation inducing capacity. Expression of cell adhesion molecules and integrin receptors tends to be down-regulated in carcinoma cells. Alterations in the expression of these proteins might not be constitutive but rather modulated by the direct environment of the tumor cell and might not only include quantitative alterations but also changes in their cell surface distribution, causing or following loss of cell polarity.

Basement Membrane↗
PubMed1992

Association of aneuploidy in index adenomas with metachronous colorectal adenoma development and a comparison.

BACKGROUND: Features of index adenomas in the colorectum may be important for the prediction of metachronous adenoma development. METHODS: Complete colonoscopic follow-up for a mean period of 10 years was achieved in 70 of 124 patients after endoscopic polypectomy of an adenoma from the colorectum. On the basis of the clinical outcome, the patients were divided into three groups: Group I, patients who had a colorectum free of adenomas and cancer; Group II, patients who had one or more metachronous adenomatous polyps; and Group III, patients who subsequently had a colorectal carcinoma. The clinical characteristics of the patients were collected, and the neoplastic specimens were re-examined with regard to pathologic parameters and flow cytometrically determined nuclear DNA content. RESULTS: Aneuploid stemlines were found in 35% of the index adenomas. Significantly more aneuploid adenomas were found in the index adenomas of Group I patients than in the adenomas of Group II patients (r = -0.20; P = 0.05). However, in the index adenomas of Group II patients, aneuploidy was associated with villous architecture (P < 0.05) and inversely related to cellular atypia (P < 0.05). Such relations were not found in the adenomas from Group I. In addition, in the Group II adenomas, aneuploidy was found frequently in the more proximally localized adenomas in the large intestine. Remarkably, all adenocarcinomas of the Group III patients were localized in the right colon. No significant differences were found in ploidy and mean DNA index between index adenomas and metachronous adenomas of the Group II patients. However, the ploidy class of the index adenomas was found not to be related to that of the metachronous adenomas in the individual patients. CONCLUSIONS: These results demonstrate that DNA cytometry in adenomas alone is not helpful in the prediction of the possibility of the development of a metachronous adenoma. However, aneuploidy in a villous adenoma located more proximally in the colon might indicate a higher risk for metachronous neoplasia development. Index and metachronous adenomas are similar in DNA content but show no relation with respect to ploidy class.

Adenoma↗