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F T Bosman

Publications and source records attributed to F T Bosman.

At least 73 records · Page 4Linked to original sources

Prevention of colorectal cancer. Costs and effectiveness of sigmoidoscopy.

There is increasing evidence that endoscopic polypectomy is a very effective means of preventing colorectal cancer. The feasibility of population-wide endoscopic screening is not established, however. The appearance of adenomatosis around the age of 60 in one-third of the population, many years prior to the manifestation of significant numbers of colorectal cancers, and the observation that the risk of developing metachronous adenomas correlates with pre-existing numbers of adenomas per colon suggest that a baseline endoscopy at 60 years with minimal follow-up may be a feasible screening strategy with a high rate of primary prevention in average risk individuals. Projections were made of the costs and benefits of various scenarios. A key element of this analysis was the assessment of probabilities to develop metachronous adenomas as a function of prior adenoma status by a mathematical approach using autopsy data. A screening strategy consisting of a baseline sigmoidoscopy at 60 years with follow-up restricted to 6% of the population was estimated to prevent 50% of colorectal cancers occurring after 60 years. A range of alternative scenarios, giving rates of primary prevention of colorectal cancer from 40 to 70%, had costs which were comparable to those of breast-cancer screening, but was far superior considering effectivity.

Adenomatous Polyposis Coli↗

A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms.

To identify new molecular markers for differentiation of normal and neoplastic colon epithelium, we have studied changes in gene expression during the in vitro differentiation of the HT29-D4 colon carcinoma cell line. Using a modified differential display procedure, we cloned a novel cDNA, designated differentiation-related gene 1 (Drg1). Drg1 mRNA has a length of approximately 3 kb and is induced approximately 20-fold during in vitro differentiation of the colon carcinoma cell lines HT29-D4 and Caco-2. The absence of Drg1 induction in growth-inhibited A431 epidermoid carcinoma cells indicates that Drg1 up-regulation in colon carcinoma cells is not a result of decreased proliferation. The Drg1 cDNA contains an open-reading frame of 1182 bp that encodes a protein with a predicted molecular weight of 43 kd. Drg1 mRNA is expressed most prominently in placental membranes and prostate, kidney, small intestine, and ovary tissues. Compared to normal colon mucosa, Drg1 mRNA expression is decreased in colon adenomas and adenocarcinomas. An antiserum raised against recombinant Drg1 protein detected a band of the expected size in Western blots. Immunohistochemistry showed that in normal colon Drg1 protein is expressed in the cytoplasm and basolateral membranes of surface epithelial cells that border the gut lumen, indicating that Drg1 protein is expressed late during differentiation, just before apoptosis and shedding of cells into the colon lumen.

Amino Acid Sequence↗

Interphase cytogenetics of prostatic tumor progression: specific chromosomal abnormalities are involved in metastasis to the bone.

Only limited data are available on chromosomes specifically involved in the multistep tumorigenesis of prostate cancer. To investigate the cytogenetic status at different stages of prostatic tumor development, we have applied interphase in situ hybridization (ISH) with a set of (peri) centromeric DNA probes--specific for chromosomes 1, 7, 8, and Y--to routinely processed tissue sections of prostatic specimens from 75 different individuals. Our panel consisted of: 16 normal/benign prostatic hyperplasia specimens; 23 primary, localized, prostatic tumors (N0M0 stage); 20 regional lymph node metastases (M0 stage); and 16 distant metastases. Numerical aberrations of at least one chromosome were not observed in normal/benign prostatic hyperplasia cases, but were present in localized tumors (39%), regional lymph node metastases (40%), and distant metastases (69%). Within the different pTNM groups, we observed the following aberrations (listed, within each series, in decreasing order of frequency): -Y, +8, -8, +7 in primary tumors; +8, +7, -Y, +Y, -8 in regional lymph node metastases; and +8, +7, +1, -Y, -8 in distant metastases. In primary tumors, the number of aberrant cases increased significantly with local tumor stage (p < 0.05). A significant increase in gain of chromosome 8 was also observed (p < 0.02). Gain of chromosome 7 and/or 8 showed a significant increase with progression of local tumor stage (p < 0.02). Specific involvement of chromosome 8 was seen in bone metastases, but not in hematogenous metastases to other sites (p = 0.02). Comparative genomic hybridization analysis of these bone metastases disclosed centromere 8 gains as amplifications of the (whole) 8q arm, whereas centromeric loss appeared to be due to loss of 8p sequences. With progression toward metastatic disease, an accumulation of genetic changes was seen as exemplified by gain of chromosome 1, which was solely observed in distant metastases. With tumor progression, gain of chromosomes 7 and/or 8 significantly increased (p = 0.03), whereas the number of cases with aberrations of the Y chromosome did not change. Furthermore, ploidy status determined by ISH revealed a significant increase in the number of aneuploid cases along with advancement of pTNM stage (p = 0.04). Collectively, the data strongly suggest that: (a) gain of chromosome 7 and/or 8 sequences is implicated in prostatic tumor progression; (b) gain of chromosome 8 sequences is related to local tumor growth; (c) overrepresentation of 8q sequences, most likely by isochromosome 8q formation, is involved in metastatic spread to the bone; and (d) changes in the centromeric copy number, as detected by interphase ISH, might in some cases represent structural alterations, such as an isochromosome.

Aged↗

Neuroendocrine cells in non-endocrine tumors: what does it mean?

In many human neoplasms histochemical techniques will demonstrate the presence of neuroendocrine cells. Their occurrence also in metastases indicates clearly that they form an integral part of the tumor cell population. As to their origin, for most tissues in which neuroendocrine cells normally occur, such as the digestive tract, the currently held view is that one stem cell population provides a repertoire of differentiation corresponding to all cell types which normally occur in that epithelium. Transformation of such a stem cell will give rise to a tumor stem cell in which the same repertoire of differentiation, including neuroendocrine cells, can be found. The tumor neuroendocrine cells usually express neurohormonal peptides corresponding to their normal counterparts. These cells almost never lead to clinically manifest overproduction of neurohormonal peptides. In other tissues, such as the normal ovary, neuroendocrine cells do not occur and yet in tumors, e.g. ovarian mucinous cystadenomas and cystadenocarcinomas, they can be found. In the epithelial components of ovarian and testicular teratomas neuro-endocrine cells have also been detected. In spite of the biological interest of this phenomenon its clinical significance remains an open question. Several investigators have found that colorectal cancers with neuroendocrine differentiation behave more aggressively than tumors without these cells. Others dispute these observations. In the breast and in the prostate neuroendocrine differentiation has been very extensively investigated and there seems to be a reasonable consensus that their presence is associated with poorer prognosis.

Cell Differentiation↗

Comparison of automated and manual analysis of interphase in situ hybridization signals in tissue sections and nuclear suspensions.

In this study we compared visual and automated analyses of interphase in situ hybridization (ISH) signals in five prostatic tumor specimens and one normal prostate sample, both in tissue sections and nuclear suspensions. The advantage of tissue sections is preservation of tissue morphology allowing precise analysis of tumor cells only. The advantage of nuclear suspensions is easier access to automated analysis, due to their disaggregated and dispersed cellular appearance. The samples were hybridized with probes for the (peri)centromeric regions of chromosome 1 and Y. The number of ISH signals per nucleus was counted both manually and automatically by means of a commercially available image analysis system. After image analysis the results were interactively corrected using a gallery display. The automatic and manual counts, before and after interactive correction, were then statistically evaluated. We found no significant differences in overall distributions between the automated and the manual counts, before as well as after correction. This was observed for both tissue sections and cellular suspensions. It is therefore concluded that automated analysis of ISH signals is feasible in both nuclear suspensions and in tissue sections, despite a low percentage of nuclei that could be measured on the latter.

Adenocarcinoma↗

Expression of nucleophosmin/B23 in normal and neoplastic colorectal mucosa.

Nucleophosmin/B23 is a 38 kD molecular phosphoprotein involved in ribosome assembly and transport. In view of the fact that nucleophosmin/B23 appears to be more abundant in tumour cells than in normal cells, the mRNA expression and immunohistochemical localization of nucleophosmin/B23 were investigated in 19 samples of non-neoplastic mucosa, six adenomas, and 16 adenocarcinomas of the colorectum. Northern blot analysis revealed that nucleophosmin/B23 mRNA is expressed at a higher level in adenomas and carcinomas than in non-neoplastic mucosa of the colorectum. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections after microwave antigen retrieval, using a nucleophosmin/B23-specific monoclonal antibody, showed almost exclusively diffuse nuclear reactivity of a majority of the epithelial cells in non-neoplastic mucosa: in adenomas, reactivity was almost exclusively nucleolar and in carcinomas, nuclear as well as nucleolar staining was observed. During mitosis, the immunoreactivity of nucleophosmin/B23 appears in the cytoplasm. The results indicate that the expression of nucleophosmin/B23 is higher in neoplastic than in non-neoplastic colorectal mucosa. Furthermore, the pattern of nucleophosmin/B23 expression shifts from nuclear to nucleolar early in the adenoma-carcinoma sequence. The exact function of nucleophosmin/B23 in colorectal carcinogenesis remains to be determined.

Adenocarcinoma↗

Expression of Bcl-2 protein in hyperplastic polyps, adenomas, and carcinomas of the colon.

The proto-oncogene Bcl-2 encodes a protein that protects cells from programmed cell death (apoptosis). The protein is expressed in the proliferative compartment of several normal tissues, including normal colonic crypts. The aim of this study was to test Bcl-2 expression in colorectal neoplasms, assuming that, as a regulator of apoptosis, it might be involved in the progression from adenoma to carcinoma. To this end, Bcl-2 reactivity was tested by immunohistochemistry in hyperplastic polyps, colonic adenomas, and carcinomas and its expression was compared with staining for the proliferation-associated Ki-67 antigen, using the MIB-1 antibody. Bcl-2 expression occurred in 2 out of 10 hyperplastic polyps and in 31 out of 35 (tubular, villous, and tubulovillous) adenomas, irrespective of their degree of dysplasia. Of ten carcinomas, only three were focally Bcl-2-positive, all moderately to well differentiated. In two of four carcinomas in Bcl-2-positive adenomas, no Bcl-2 staining was observed. High numbers of MIB-1-positive cells were found in all hyperplastic and neoplastic lesions, without apparent correlation between proliferation and Bcl-2 expression. These findings suggest that in the pathogenesis of hyperplastic polyps, increased crypt cell proliferation is primarily involved, but in some lesions decreased apoptosis may play a role. Furthermore, the increased Bcl-2 expression in adenomas but not in the majority of the carcinomas suggests either that decreased apoptosis is not usually involved in the pathogenesis of these lesions or that the regulation of apoptosis in colorectal epithelia involves additional regulatory factors.

Adenoma↗

New curricula.

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Cost-Benefit Analysis↗

A new monoclonal antibody for specific immunocytochemical staining of nucleoli.

We have isolated a hybridoma cell line (clone 1E10) producing a monoclonal antibody which specifically recognizes nucleoli. The antibody (IgM, k isotype) was found to react in a nucleolar pattern with a variety of cell types. Specific staining was only obtained on cryostat sections of unfixed tissues. Paraffin embedding destroyed the epitope. Tissue specificity or species specificity was not observed. Nucleoli in neoplastic cells were highly reactive, presumably due to the larger size of nucleoli in these cells. Immunoelectron-microscopy (using a pre-embedding as well as a post-embedding technique) confirmed the specific nucleolar localization of the immunoreactivity. Immunoreactivity was confined to the granular component of the nucleolus. The intensity of the immunoreactivity increased after cell or tissue pretreatment with DNase, pronase or trypsin, indicating that the target epitope is not DNA or a protein. On Western blots of immunoreactive cells no specific signal was obtained, which supports the non-protein nature of the epitope. Acid hydrolysis and RNase digestion abolished the immunoreactivity. Parallel staining experiments with methylgreen pyronin and acridin orange confirmed the RNA nature of the epitope. In spot blots, immunoreactivity was not found with tRNA or mRNA. These observations indicate that 1E10 recognizes a conformational RNA epitope which occurs only in the nucleolus.

Animals↗

p21ras in carcinogenesis.

The activation of p21ras proteins is required in signal transduction pathways that lead to cell proliferation. More recently, a role for p21ras proteins has also been suggested in pathways to apoptosis and in the regulation of the cell cycle. Pointmutated p21ras oncogenes code for constitutively activated p21ras proteins, which disturb the balance between cell growth and cell death in favour of cell growth. In this way, p21ras oncoproteins may contribute to carcinogenesis. The binding of growth factors to their receptors triggers a cascade of protein interactions, including activation of the p21ras proteins. In turn, p21ras proteins set the machinery for cell division in motion by stimulating different effector proteins which regulate the morphological alterations, the nutritional requirements, and the changes in gene expression necessary for cell division. The presence of p21ras oncoproteins constitutively stimulate proliferation, whilst the apoptotic pathway is suppressed along with the loss of cell cycle regulation. This review describes the function of the p21ras proteins in signal transduction pathways that control proliferation and apoptosis, and regulate the cell cycle. The dysregulation of these signal transduction pathways due to the presence of p21ras oncoproteins is discussed in the context of early carcinogenesis.

Animals↗

Apoptosis: pathophysiology of programmed cell death.

In all normal tissues, cell proliferation and cell death are balanced. The physiology of normal cell death, which has become generally known as apoptosis or programmed cell death, has been intensely investigated in recent years. In this review the cell biology and biochemistry of apoptosis are discussed. Although apoptotic cells can be morphologically recognized, characteristic molecular features such as internucleosomal DNA fragmentation, and histochemical techniques such as in situ end labeling, facilitate the recognition of apoptosis. Many of the genes involved in the regulation of apoptosis, which include cell growth associated genes such as c-myc and p53, have been identified. It has become clear that the bcl-genes (more explicitly bcl-2 and bax) are important apoptosis regulators. The details of the mechanism of programmed cell death are, however, not completely unraveled. It has become clear that apoptosis plays an important role in organ and tissue development during embryogenesis. Examples are the morphogenesis of limbs from limb buds, the development of the central nervous system and the maturation of the hematopoietic and lymphatic systems. Hormonal regulation of cells and tissues is also partly executed through apoptosis. In a variety of disease apoptosis plays a role. In cancer, apoptosis is a crucial feature, and in the resolution of inflammatory reactions, apoptosis is essential. In neurodegenerative diseases, dysregulation of the cell death programme may play a role. Further elucidation of the role of apoptosis in these diseases may lead to new possibilities for treatment.

Animals↗

Expression of the multidrug resistance-associated protein (MRP) gene in primary non-small-cell lung cancer.

BACKGROUND: One of the major problems in the cure of advanced non-small-cell lung cancer (NSCLC) is its lack of response to cytotoxic drug treatment, and the mechanisms underlying this intrinsic drug resistance are unclear. PATIENTS AND METHODS: We determined the expression of a newly recognised drug resistance gene, the Multidrug Resistance-associated Protein (MRP) gene, in normal lung tissue and in tumour biopsies from 35 surgically resected NSCLCs (11 adenocarcinomas, 24 squamous cell carcinomas). MRP mRNA levels were quantitated by RNase protection assay and expression of the MRP Mr 190,000 glycoprotein was estimated by immunohistochemistry. RESULTS: Using the MRP-specific monoclonal antibody MRPr1, MRP expression was detected by immunohistochemistry in epithelial cells lining the bronchi in normal lung. In NSCLC approximately 35% of the samples showed elevated MRP mRNA levels. Based on MRP-specific immunohistochemical staining the tumours were divided into 4 groups: 12% were scored as negative (-), 14% showed weak cytoplasmic staining of the tumour cells (+/-), 40% had a clear cytoplasmic staining (+), and in 34% a strong cytoplasmic as well as membranous staining was observed (++). MRP expression, as estimated by immunohistochemistry, correlated with the MRP mRNA levels quantitated by RNase protection assay (correlation coefficient = 0.745, p = 0.0009), with MRP mRNA levels (mean +/- SD) of 3.0 +/- 1.0 U, 3.5 +/- 0.7 U, 7.5 +/- 5.9 U, and 19.3 +/- 10.7 U, in the (-), (+/-), (+), and (++) immunohistochemistry expression groups, respectively. Among the squamous cell carcinomas a correlation was observed between MRP staining and tumour cell differentiation: the strongest MRP staining was predominantly found in the well differentiated tumours. CONCLUSIONS: Hyperexpression of MRP is frequently observed in primary NSCLC, especially in the well differentiated squamous cell carcinomas. Further studies are needed to assess the role of MRP in the mechanism of clinical drug resistance in NSCLC.

ATP-Binding Cassette Transporters↗

The use of somatostatin receptor scintigraphy in the differential diagnosis of pancreatic duct cancers and islet cell tumors.

OBJECTIVE: In the present study, the diagnostic value of somatostatin receptor scintigraphy (SRS) was evaluated in the preoperative workup in patients with pancreatic duct cancers and islet cell tumors, as well as in the follow-up of these patients. METHODS: Twenty-six patients with suspected primary pancreatic duct cancers and 48 patients with islet cell tumors were studied. The SRS was performed using the radionuclide-labeled somatostatin analogue 111In-octreotide. Another group of 12 patients who were still alive more than 3 years after pancreaticoduodenectomy for pancreatic duct adenocarcinomas also underwent SRS. RESULTS: In 31 (65%) of 48 patients, the primary pancreatic islet cell tumor as well as its often previously not yet recognized metastases could be visualized. In contrast, none of the 26 pancreatic adenocarcinomas or their metastases could be seen. In 5 of 12 patients who were alive more than 3 years after pancreaticoduodenectomy for pancreatic duct adenocarcinomas, metastatic lesions were visualized at SRS. In retrospect, these patients were not operated on for adenocarcinomas but for "nonfunctioning" islet cell tumors. CONCLUSIONS: The present study supports the concept that SRS has a place in the preoperative differential diagnosis of islet cell tumors and pancreatic duct cancers as well as in the follow-up, especially in those cases in which no tumor histologic analysis was obtained, or the pathologic examination of the tumor tissue had not included special staining procedures for neuroendocrine characteristics. Our results also indicate that the evaluation of the results of investigations on the role of surgery or radiation therapy and chemotherapy or both in pancreatic duct cancer have to be interpreted with caution, if no histologic analysis and staining for neuroendocrine characteristics was performed.

Adenocarcinoma↗

Immunohistochemical, morphological and ultrastructural resemblance between dendritic cells and folliculo-stellate cells in normal human and rat anterior pituitaries.

Immunolabeling of cryo-sections of human anterior pituitaries obtained at autopsy, and of cryo-sections of freshly prepared rat anterior pituitaries, with a panel of monoclonal antibodies against markers of the monocyte/dendritic cell/macrophage lineage, reveals in both species a characteristic pattern of immunopositive cells, among which many cells with dendritic phenotype are found. Cells characterized by marker expression of MHC-class II determinants and a dendritic morphology are present in both human and rat anterior pituitary. Markers characteristic of dendritic cells such as the L25 antigen and the OX62 antigen were present in anterior pituitaries from human and rat respectively. The population of MHC-class II expressing dendritic cells of the rat anterior pituitary is compared at the ultrastructural level with the folliculo-stellate cell population, which cell type has been previously characterized by its distinctive ultrastructure and immunopositivity for the S100 protein. Using immuno-electron microscopy of rat anterior pituitaries fixed with periodate-lysine-paraformaldehyde, we were able to distinguish non-granulated cells expressing MHC-class II determinants, whereas no MHC-class II expression was found in the granulated endocrine cells. Using double immunolabeling of cryo-sections of these rat AP with 25 nm and 15 nm gold labels, we demonstrated an overlap between the populations of MHC-class II-expressing and S100 protein-expressing cells. Furthermore, MHC-class II-expressing and S100-positive cells showed ultrastructural characteristics that have been previously ascribed to folliculo-stellate cells. At the light microscopical level in the rat AP, a proportion of 10 to 20% of the S100-positive cells was found immunopositive for the MHC-class II marker OX6. In the human AP, S100-positive folliculo-stellate cells and cells expressing the leukocyte common antigen CD45 were found to occupy predominantly different tissue compartments in the human anterior pituitary, namely the epithelial parenchyme cords and perivascular compartments respectively. A proportion of CD45+ cells was found in the parenchyme compartment and, vice versa, indicating an overlap of the tissue compartments in which both cell types occur. However, at the light microscopical level we could not find cells expressing both the S100 and CD45 marker. The present finding of a proportion of S100-positive pituitary cells with ultrastructural and immunohistochemical characteristics of both dendritic cells and folliculo-stellate cells, confirms the suggested heterogeneity of the latter cell group with respect to their ultrastructural phenotype and putative function. The possibility of a myeloid origin of part of the folliculo-stellate cell group in the AP, is discussed and might elucidate some of the discrepancies in the literature concerning the embryological origin of this cell group.

Adult↗

Regional metastasis in head and neck squamous cell carcinoma: revised value of US with US-guided FNAB.

PURPOSE: To verify the acclaimed accuracy of ultrasound (US) combined with US-guided fine-needle aspiration biopsy (FNAB) in the detection of lymph node metastasis in the neck and to evaluate the interobserver variability. MATERIALS AND METHODS: In a prospective, multicenter study of 185 patients with head and neck squamous cell carcinoma, US (n=238 neck sides) with US-guided FNAB (n=178 neck sides) was used for evaluation of the lymph node status of the neck. Findings were correlated with those of histopathologic examination in 238 neck sides. RESULTS: US with US-guided FNAB had a sensitivity of 77% and a specificity of 100%. Nineteen of 178 aspirations were nondiagnostic. There were no significant differences between the four participating hospitals or the individual sonologists (P>.05). CONCLUSION: Sensitivity of US with US-guided FNAB was slightly lower compared with previous reports. Specificity was similar to previous reports. Interobserver variability appeared to be low. The validity of US with US-guided FNAB is high and warrants widespread use of the procedure for evaluation of the neck.

Adult↗