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F T Bosman

Publications and source records attributed to F T Bosman.

At least 19 recordsLinked to original sources
PubMed1995

Accumulation of genetic abnormalities during neoplastic progression in Barrett's esophagus.

Sex chromosome status, ploidy, and proliferation rate were evaluated in archival material of 73 Barrett's esophagus patients (48 males and 25 females). Diagnosis in esophageal mucosa samples ranged from intestinal metaplasia with no dysplasia to invasive esophageal adenocarcinoma; also, four lymph node metastases were studied. Chromosomal and ploidy aberrations were determined by in situ hybridization with repetitive DNA probes specific for chromosomes Y, X, and 1. Proliferation index (Ki-67 protein expression) was assessed by immunohistochemistry. Proliferation rate was elevated in all stages of dysplasia and in the adenocarcinomas. Aneuploidy (hyperdiploidy) and loss of the Y chromosome correlated with the advancing stages toward neoplasia (P < 0.001) and reached high prevalences (70-100%) in high-grade dysplasia and adenocarcinoma. Abnormalities of the X chromosome were not seen. These data suggest that in Barrett's esophagus, genetic perturbations may be generated in relation to a high proliferation rate.

Adenocarcinoma↗
PubMed1995

Interphase cytogenetics of prostatic adenocarcinoma and precursor lesions: analysis of 25 radical prostatectomies and 17 adjacent prostatic intraepithelial neoplasias.

Twenty-five radical prostatectomy specimens were screened for the presence of numerical chromosome changes within the adenocarcinoma as well as 17 adjacent prostatic intraepithelial neoplasias (PIN) by means of interphase in situ hybridization (ISH) to routinely processed tissue sections. To this end a defined alfoid repetitive DNA probe set was used, specific for the centromeres of chromosomes 1, 7, 8, 10, 15, and Y. The cytogenetic information was correlated with histopathological and clinical features as well as with DNA ploidy. Numerical aberrations of at least one chromosome were shown in 13 of 25 cases (52%). Alterations of chromosome 8 and loss of the Y chromosome were the most frequent findings (both 20%), followed by loss of chromosomes 15 (16%) and 10 (12%). Gain of chromosome 7 was seen in 8% of cases. No aberrations of chromosomes 7, 8, 10, and 15 were found in the adjacent PIN lesions, whereas loss of the Y chromosome in both PIN and tumor occurred in two cases. Also, (low level) aneuploidy was observed in 76% of these PIN lesions. Ploidy of the carcinomas as assessed by ISH correlated well with ploidy measured by DNA flow cytometry (FCM; P < 0.02). Due to the more specific correspondence between ISH and tumor pathology, pathologic grade correlated with ISH aneuploidy (P < 0.05), whereas FCM ploidy did not. Furthermore, genetic heterogeneity within a tumor was seen, as judged by the focal appearance of chromosomal aberrations. Chromosomal alterations occurred in all grades and stages, although loss of chromosome 10, gain of chromosome 7, and aberrations of chromosome 8 tended to predominate in more advanced cancers.

Adenocarcinoma↗
PubMed1995

Accumulation of p53 protein in normal, dysplastic, and neoplastic Barrett's oesophagus.

Accumulation of p53 protein was determined by immunohistochemistry in archival material of biopsy specimens from 102 patients with Barrett's oesophagus with different grades of dysplasia, in 24 oesophageal adenocarcinomas associated with Barrett's oesophagus, and in 23 cases of metaplastic epithelium adjacent to these carcinomas. Immunostaining for the p53 protein was found in 23/102 (23 per cent) cases of the Barrett's oesophagus biopsies and in 12/23 (52 per cent) cases of Barrett's oesophagus adjacent to adenocarcinoma. Significant correlations were found between the grade of dysplasia and p53 immunoreactivity in both Barrett's biopsies without adenocarcinoma (P < 0.001) and Barrett's oesophagus adjacent to adenocarcinoma (P < 0.05). In the adenocarcinomas, intense nuclear immunohistochemical staining for p53 was diffusely or focally present in 20/24 (83 per cent) of the specimens. In Barrett's oesophagus, p53 is a progression marker with high expression in high-grade dysplasia (89 per cent) and adenocarcinoma (83 per cent).

Adenocarcinoma↗
PubMed1995

Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary.

The most common carcinomas metastatic to the ovary that mimic ovarian primaries are colonic adenocarcinomas and endometrial carcinomas. Conventional histochemical staining procedures, even in combination with additional immunohistochemical assays, are of limited value in distinguishing between these metastases and primary ovarian carcinomas. In this study we investigated whether the application of monoclonal antibodies against keratins 7, 8, and 20 could help in differentiating between these categories. The reactivity patterns of 40 carcinomas metastatic to the ovary were compared with those of their primary carcinomas on the one hand and with various primary ovarian carcinomas and mesotheliomas on the other. Colon cancer metastatic to the ovary was keratin 7 negative and keratin 20 positive in 94% of the cases; in contrast, all primary ovarian carcinomas were keratin 7 positive and keratin 20 negative, with the exception of two cases of mucinous cystadenocarcinoma. Ovarian metastases of gastric cancer usually contained keratins 7 and 20. Metastases of endometrial cancer to the ovary and primary ovarian carcinomas usually showed similar keratin expression. We propose that keratin 7 and 20 antibodies may be of help to distinguish between primary ovarian carcinomas and carcinoma metastases in the ovary.

Adenocarcinoma↗
PubMed1995

Neural cell adhesion molecule distribution in primary and metastatic uveal melanoma.

Tumor cell adhesion, detachment, and aggregation play an important part in tumor invasion and metastasis, and a variety of cell adhesion molecules have been found on tumor cells. Cell adhesion molecules, including those of the immunoglobulin superfamily, are associated with the development of metastatic behavior in cutaneous melanomas. The neural cell adhesion molecule (NCAM) belongs to this family. To investigate its possible role in the development metastatic behavior of uveal melanomas, the authors studied immunohistochemically the expression of NCAM by using an antibody that recognizes all three major isoforms of NCAM and an antibody that recognizes the HNK-1 epitope present on some isoforms of NCAM. The authors studied 32 primary uveal melanomas from 32 patients (among these, 12 were rapidly metastasizing and 16 slowly metastasizing) and 29 metastases from 19 patients. From 13 patients the primary, as well as the metastatic, tumors were available. With one exception, all HNK-1 positive primary and metastatic tumors were also positive for NCAM. NCAM was significantly more expressed in aggressive, rapidly metastasizing primary tumors (P = .02 and .04, respectively) and in metastases. HNK-1 was significantly (P = .04) more expressed in larger tumors. In liver metastases HNK-1 immunoreactivity was significantly (P = .005) less frequently expressed than NCAM. Therefore, NCAM isoforms that lack the HNK-1 epitope might play a role in the organ specific metastatic behavior of uveal melanomas.

Antibodies, Monoclonal↗
PubMed1995

In vivo and in vitro invasion in relation to phenotypic characteristics of human colorectal carcinoma cells.

In this study we investigated the tumorigenicity, growth pattern and spontaneous metastatic ability of a series of nine human colorectal carcinoma cell lines after subcutaneous and intracaecal xenografting in nude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumorigenic in either site; the other cell lines were tumorigenic in both sites. SW1116, SW480 and SW620 did not show local invasive in the NCI-H716 and LS174T cells were both invasive in the caecum, but only NCI-H716 was invasive in the subcutis. HT29 and 5583 (S and E) cells were invasive in the caecum and from that site metastatic to the lungs and/or the liver. HT29 and 5583S cells were both invasive in the subcutis, but 5583E cells were not. Of each category of in vivo behaviour in the caecum, one cell line was further investigated with regard to invasion in vitro (into embryonic chick heart fragments), E-cadherin expression in vivo and in vitro and in vitro production of u-PA and t-PA. These parameters were chosen in view of their purported role in extracellular matrix degradation and intercellular adhesion, which are all involved in the invasive and metastatic cascade. Invasion in vitro was not predictive for invasion or metastasis in vivo. In the cell line which showed invasion in embryonic chick heart tissue, heterogeneous E-cadherin expression was observed in vitro together with a relatively high production of u-PA. The non-invasive cell lines showed in vitro homogeneous expression of E-cadherin with a relatively low production of u-PA. In vivo expression of E-cadherin was either absent or heterogeneous. We conclude that: (1) colorectal carcinoma xenografts show site-specific modification of in vivo invasive and metastatic behaviour; (2) invasion in vitro does not correlate with invasion and metastasis in vivo; (3) in vitro non-invasion might be associated with homogeneous E-cadherin expression and low production of u-PA; (4) E-cadherin expression in vitro differs from E-cadherin expression in vivo. The results support the notion that the microenvironment in which cancer cells grow is one of the factors involved in the regulation of invasive and metastatic behaviour.

Animals↗
PubMed1995

Immunohistochemical and prognostic analysis of apoptosis and proliferation in uveal melanoma.

Neoplasia can be defined as deregulated tissue homeostasis caused by an imbalance between proliferation and apoptosis. Many genes are involved in the maintenance of tissue homeostasis, eg, the c-myc oncoprotein, which is an important regulator of cell proliferation and Bcl-2 protein, which is involved in the regulation of apoptosis. We studied retrospectively indices of proliferation, such as mitotic count and the Mib-1 index, on 51 uveal melanomas and compared their prognostic significance with established indicators of prognosis such as cell type and tumor size. Along the same line we investigated the expression of the regulating proteins c-myc and Bcl-2. Of all parameters tested, the largest tumor diameter and mitotic count were most strongly associated with tumor-related death (P < 0.001 and P = 0.005, respectively). In addition, cell type, the presence of epithelioid cells, the Mib-1 index, and the percentage of cytoplasmic c-myc-positive cells were significant predictive factors. Multivariate analysis showed that the Mib-1 index, largest tumor diameter, and the percentage of cytoplasmic c-myc-positive cells were independent prognostic parameters. Bcl-2 expression did not correlate with clinical outcome. The Mib-1 index correlated with the presence of epithelioid cells (P < 0.03) and the presence of apoptotic bodies (P < 0.001) and c-myc. A strong inverse relationship was found between (nuclear and cytoplasmic) c-myc and Bcl-2 (P < 0.00004 and P < 0.006, respectively), suggesting that Bcl-2 cooperates with c-myc to immortalize uveal melanoma cells.

Apoptosis↗
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↗
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↗
PubMed1992

Renewal of enterochromaffin cells in the rat caecum.

The localization, morphology, and neurohormonal peptide content of neuroendocrine cells have been extensively investigated. Relatively little is known about the kinetics of growth and differentiation of these cells. We studied the kinetics of enterochromaffin (EC) cells in the caecum of the rat, by applying the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), to identify cells in S-phase, administered in pulse-chase and synchronous continuous labeling experiments. By double indirect immunofluorescence staining of tissue sections, using antibodies against serotonin and BrdU, percentages of BrdU positive EC cells could be enumerated, from which cell-kinetic parameters were derived. The following conclusions were drawn: 1) EC cells are renewed by proliferation of EC cells and by recruitment from proliferating precursor cells. 2) Caecal EC cells appear to consist of a relatively rapidly renewing and migrating fraction (60-65%) with a turnover time of approximately 16 days and a relatively slowly renewing and possibly stationary fraction (35-40%) with an estimated turnover time of approximately 150 days. 3) Seventy percent of the EC cells are localized in the lower half of mucosal crypts, 30% in the upper half. After prolonged labeling the percentage of labeled EC cells in the lower crypt half always exceeds that in the upper crypt half. This decrease in labeled EC cells during migration towards the mucosal surface indicates loss of endocrine cells, possibly owing to loss of endocrine characteristics.

Animals↗
PubMed1992

Oestrogen and progesterone receptor immunocytochemistry in human hyperplastic and neoplastic endometrium.

Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions between stromal and epithelial cells. To determine whether the stromal-epithelial relation with respect to oestrogen receptor (OR) and progesterone receptor (PR) is disturbed in (pre)malignant endometrium immunocytochemical OR and PR expression was quantitated by computerized image analysis. This was studied in the stromal and epithelial cells of endometrial specimens diagnosed as hyperplasia (n = 14), atypical hyperplasia (n = 16), and adenocarcinoma (n = 33). Paraffin sections were used for optimal preservation of histomorphology. A progressive loss of OR and PR content occurred with increasing malignant transformation. Stromal cells in atypical hyperplasia (P = 0.0007) and well-differentiated adenocarcinoma (P = 0.0008) exhibited a relative loss of PR content as compared with epithelial cells (P = 0.036 and P = 0.17, respectively). In atypical hyperplasia, the decrease in stromal PR content was not in parallel with persistent stromal OR immunostaining. Furthermore, stromal PR expression in atypical hyperplasia was significantly (P = 0.004) lower than in the surrounding hyperplasia, whereas the stromal OR staining as well as the epithelial OR and PR staining did not differ significantly. These observations may reflect a disturbance in hormonal interrelationships between endometrial cells in the development of endometrial neoplasia, indicating that stroma may modulate epithelial growth by paracrine mechanisms.

Adenocarcinoma↗
PubMed1992

L-CAM expression in normal, premalignant, and malignant colon mucosa.

L-CAM is a cell adhesion molecule which is expressed at the intercellular borders of most epithelial cells. L-CAM has been demonstrated to act as an invasion suppressor in carcinoma cell lines. In order to determine whether or not L-CAM expression might distinguish between invasive and non-invasive or metastatic and non-metastatic colon neoplasms, we studied L-CAM expression in normal colon mucosa, colon adenomas with various degrees of dysplasia, and colon carcinomas by immunohistochemistry, using the 6F9 monoclonal anti-L-CAM antibody. Normal mucosa showed evenly distributed distinct L-CAM immunoreactivity along intercellular borders. In adenomas and carcinomas, a similar though weaker expression was observed. This pattern showed a tendency to decrease in parallel with decreasing differentiation. However, no correlation was found with Dukes stage or area within the tumour. In some carcinomas, L-CAM was expressed at the luminal surface of the cells. In others, L-CAM expression was not found. These results suggest that L-CAM expression is disregulated or lost as an early event in the development of colon neoplasia and indicate that L-CAM expression does not correlate with invasive or metastatic potential.

Adenoma↗
PubMed1992

Does ex vivo labelling of proliferating cells in colonic and vaginal mucosa reflect the S-phase fraction in vivo?

The ex vivo labelling of DNA-synthesizing epithelial cells in colonic and vaginal mucosa was compared with in vivo labelling. For this purpose, in vivo S-phase cells were labelled with [3H]thymidine (Tdr) and ex vivo labelling was continued by culturing tissue specimens in bromodeoxyuridine (BrdU). Various methods of tissue culture were employed in order to improve diffusion of medium (and BrdU) in the tissue. BrdU and 3H-TdR labelling were evaluated by immunohistochemistry and autoradiography respectively. Ex vivo labelling resulted in a patchy distribution of labelled cells, which did not correspond with the 3H-TdR labelling pattern obtained in vivo. Under the described conditions ex vivo labelling does not appear to be a reliable for estimation of the proliferative activities in vivo.

Animals↗
PubMed1992

Bromodeoxyuridine (BrdU) immunocytochemistry by exonuclease III (Exo III) digestion.

A new procedure is described to generate single-stranded DNA by exonuclease III (Exo III) digestion for bromodeoxyuridine (BrdU) immunocytochemistry on tissue sections. We compared this procedure with the most widely used procedure of DNA denaturation with 2 N HCl. In vivo and in vitro pulse and continuous labelling of tissues and cells were used. The specimens were fixed in formalin, ethanol, glutaraldehyde, Carnoy's, Bouin's or Zamboni's fixative and embedded in paraffin or used unfixed as cryostat sections or cytospin preparations. After Exo III digestion, BrdU substituted DNA was detected irrespective of the fixation procedure applied. The optimal protocol for nuclease digestion appeared to be simultaneous incubation, of 10 Units Exo III per ml EcoRI buffer and anti-BrdU monoclonal antibody at 37 degrees C. The advantages of Exo III digestion for BrdU immunocytochemistry compared to acid denaturation were: less non-specific nuclear background reactivity, no DNA renaturation, less DNA loss, optimal nuclear morphology, increase in antibody efficiency and the possibility for simultaneous detection of acid-sensitive tissue constituents. Disadvantages of the Exo III digestion are decreased sensitivity and the need for more rigorous pepsin pretreatment. We conclude that Exo III digestion of DNA is an appropriate alternative for acid denaturation for BrdU immunocytochemistry on sections of pulse-labelled specimens.

Animals↗
PubMed1992

NCI-H716 cells as a model for endocrine differentiation in colorectal cancer.

In colonic neoplasms, endocrine differentiation is encountered not only in carcinoid tumors but also in adenocarcinomas, where endocrine cells may represent a distinct line of differentiation in the tumor. The significance of endocrine differentiation in colorectal cancer is not well established, partly because of the paucity of tumor cell lines which can serve as a model for studying endocrine differentiation. In this report we describe the properties of NCI-H716 cells, a cell line derived from a poorly differentiated adenocarcinoma of the caecum, under various in vitro conditions and as xenografts in athymic mice. Phenotypical properties were immunohistochemically assessed using a panel of differentiation related antibodies, and also by Northern blot analysis and by electron microscopy. Receptors for biogenic amines and peptide hormones were analyzed by ligand binding assay. These studies show that: 1. NCI-H716 cells can be undifferentiated, or show endocrine, mucin-producing or "amphicrine" properties. 2. Endocrine differentiation of NCI-H716 cells preferentially occurs in xenografts in athymic mice, which suggests that mesenchymal elements induce endocrine differentiation. 3. NCI-H716 cells express large amounts of high affinity receptors for gastrin, serotonin and somatostatin and these substances can regulate growth. Thus, NCI-H716 cells form a suitable model for the study of endocrine differentiation in intestinal epithelium and of auto- or paracrine growth regulation in intestinal neoplasia.

Animals↗
PubMed1992

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results.

OBJECTIVES: The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS: Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS: Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS: Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.

Actins↗