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Biomedical subjects

G Griffioen

Publications and source records attributed to G Griffioen.

At least 109 records · Page 6Linked to original sources
PubMed1990

Neoplasia-related changes of two copper (Cu)/zinc (Zn) proteins in the human colon.

Cu/Zn-containing proteins have recently become of interest with regard to their relation with malignant disorders. Cu Zn-superoxide dismutase (Cu/Zn-SOD) was found increased in chemically induced tumors of the large bowel whereas metallothionein (MT), containing Zn and some Cu, was shown important for the response of tumors to chemotherapy. In the present study, we evaluated the Cu/Zn-SOD and MT content of normal human colonic mucosa and colorectal carcinomas, obtained from 20 resection specimens, and of 47 adenomatous polyps. The Cu/Zn-SOD content of polyps and carcinomas was significantly (p less than 0.01) elevated when compared to normal mucosa. In the adenomatous polyps the Cu/Zn-SOD content increased significantly with increasing grade of epithelial cell dysplasia, diameter, and presence of a villous component. In the carcinomas no relation was noticed between the Cu/Zn-SOD content and the Dukes' stage or the grade of differentiation. The MT content was significantly decreased in both adenomatous polyps and carcinomas when compared to that in normal mucosa. The MT content was not related to the grade of epithelial cell dysplasia of the polyps, and to the Dukes' stage or the differentiation of the carcinomas. In conclusion, neoplasia of the colorectum is accompanied by an increase in Cu/Zn-SOD and a decrease in MT. These findings support the association between changes in Cu/Zn proteins and malignancy.

Adenocarcinoma↗
PubMed1990

Solitary and synchronous adenomas of the colon and rectum: comparison of malignancy parameters.

The histological, mucin histochemical and immunohistochemical features were evaluated of 74 solitary and 73 synchronous colorectal adenomas which were endoscopically removed from 124 patients. Of the patients, 60% had a single adenoma, whereas 40% had at least two adenomas in their colorectum. Comparing the incidence of synchronous adenomas in both sexes revealed a statistically significant higher incidence (P less than 0.005) in males. The localization of the solitary and synchronous adenomas in the large bowel was similar. Moreover, parameters of malignant change within the adenomas (size, predominant type of mucosal growth and degree of dysplasia-with the exception of severe dysplasia) as well as signs of dedifferentiation (relative proportions of goblet and columnar cells) were also similar. Mucin staining intensities (periodic acid-Schiff, high iron diamine and alcian blue) and the immunoreactivity patterns of secretory component and carcinoembryonic antigen, both cytoplasmic and on the surface of the epithelial cells, were also identical in both groups of adenomas. Thus, neither the routine histological nor the mucin- and immunohistochemical features differed between the groups, except for severe dysplasia. It is concluded that there is no inherent difference in malignant potential between solitary and synchronous adenomas, with the possible exception of the degree of dysplasia.

Adenoma↗
PubMed1989

Presymptomatic diagnosis of familial adenomatous polyposis by bridging DNA markers.

Familial adenomatous polyposis (FAP) is a disorder with autosomal dominant inheritance, which predisposes to colorectal adenocarcinoma. The gene causing the disorder has been assigned to chromosome 5 by means of a polymorphic DNA marker called C11p11. An informative Dutch pedigree showed that two other linked polymorphic DNA markers, Pi227 and YN5.48, closely flank the FAP locus, one on either side. This finding will allow prenatal and presymptomatic diagnosis of FAP, with more than 99.9% reliability in the majority of families, by means of already available markers.

Adenomatous Polyposis Coli↗
PubMed1989

Mucin profiles and potential for malignancy of human colorectal adenomatous polyps.

The mucin histochemical and histologic features of 166 colorectal adenomatous polyps from 124 patients were studied. A majority of the polyps (62%) had a tubular growth pattern whereas 38% showed villous growth. Severe dysplasia was more frequently found in the latter group. A significant correlation (r = 0.27, P less than 0.001) was found between the severity of dysplasia and the size of the polyps. Moreover, the ratio between goblet and columnar cells was also found to decrease (P less than 0.0001) with the severity of dysplasia. Independent of the mucin stain used (periodic acid-Schiff, alcian blue, and high-iron diamine stains), mucin reactive cells were found to be negatively correlated (-0.17 less than r less than -0.44, P less than 0.01) with severity of dysplasia, especially in the tubular adenomas. These findings suggest that evaluation of mucin stain, related to dysplasia, may contribute to the assessment of premalignant and early malignant changes in adenomas of the colon.

Adenocarcinoma↗
PubMed1989

The expression of carcinoembryonic antigen and secretory component in adenomas of the human colon and rectum.

The immunohistochemical staining for carcinoembryonic antigen (CEA) and secretory component (SC) was evaluated in 166 endoscopically obtained colorectal adenomas of 124 patients. Expression of CEA, both in the cytoplasm and on the surface of the epithelial cells, was found to be moderately correlated with the severity of dysplasia in all adenomas. This relation was not observed with the SC expression in the adenomas. Both CEA and SC expressions were found to be increased with the size of the adenomas, but only in the villous adenomas and not in the tubular adenomas. These findings indicate that evaluation of CEA and SC expression does not add much additional information to the known parameters of malignant potential of colonic adenomas, such as dysplasia, size, and pattern of mucosal growth.

Adult↗
PubMed1989

Plasminogen activators in (pre)malignant conditions of the colorectum.

Plasminogen activators have been implicated in the process of tumour growth, invasion and metastatic spread. Recent studies indicate that urokinase (mu-PA) is the major type of plasminogen activator correlated with the evolution of adenocarcinomas of the colon. Comparable changes in the plasminogen activator profile have been found in premalignant conditions of the colon as observed in adenocarcinomas. The feasibility of determining plasminogen activators in endoscopical biopsies may provide diagnostic opportunities for the detection of early malignant changes in the human colon.

Colorectal Neoplasms↗
PubMed1989

Plasminogen activators in endoscopic biopsies as indicators of gastrointestinal cancer: comparison with resection specimens.

In resection tissue samples of colorectal carcinomas, the concentration of urokinase-type plasminogen activator (u-Pa) was found to be significantly higher than in the normal parent mucosal tissue, while there was less tissue-type plasminogen activator (t-PA). u-PA and t-PA were also determined in endoscopic biopsies of colonic and gastric carcinomas, and the results were compared with those of the ultimate resection samples of the same patients, and with the histological evaluation of adjacent biopsies. The ratio of u-PA/t-PA antigen in the biopsies was found to represent a good discriminator between normal and malignant tissue. Nearly all (90%) tumour biopsies had a higher PA antigen ratio than that of the normal tissue biopsies. This discrimination based upon PA antigen measurements in biopsies was similarly efficient in the subsequent resection samples, and showed a good agreement with the histological evaluation. Thus, PA antigen measurements in endoscopic biopsies can be used to detect gastrointestinal malignancy.

Aged↗
PubMed1988

Plasminogen activator profiles in neoplastic tissues of the human colon.

Plasminogen activator (PA) activity, in particular urokinase (u-PA), has been shown to be markedly increased in adenocarcinomas of the colon. Adenomatous polyps were found to be intermediate in their PA activity to normal mucosa and adenocarcinomas. In the present study we evaluated the PA profile in relation to malignancy parameters of the adenomas. Forty-eight adenomatous polyps, obtained by endoscopic polypectomy, were scored according to size, histological type, and grade of dysplasia. In extracts, tissue-type PA (t-PA) and u-PA were determined using a spectrophotometric enzyme assay, antigen assays, and a bioimmunoassay for u-PA. Twenty-five paired samples of normal mucosa and adenocarcinoma were used as controls. Additionally, four hyperplastic polyps were studied by the same methods. The presence of complexes of PA with PA inhibitors was assessed by zymography. A 10-fold increase of u-PA antigen in carcinomas was found as compared to normal tissue. An increase was also noted in u-PA activity, although its extent was less, due to the fact that 74% of u-PA was in the inactive proenzyme form. Adenomatous polyps contained PA activities and antigens intermediate to those of normal mucosa and carcinomas, in accordance with the view that they are precursors in the development of colorectal cancer. Within the adenoma group, no relation was found between PA profile changes and histological type or polyp size. Surprisingly, in a group of four hyperplastic polyps, similar profiles of PA were found as in adenomas. When the u-PA/t-PA antigen ratio was taken as a parameter of developing malignancy, two discrete increases were seen during the adenoma-carcinoma sequence, the first at adenoma formation and the second accompanying the start of invasive growth in polyps with severe dysplasia. Zymography showed that only t-PA was present in complex with specific PA inhibitors, explaining how the decrease of t-PA activity in adenomas and carcinomas could be stronger than the parallel decrease of t-PA antigen, when these were compared with normal mucosa, which contained hardly any complexes.

Adenoma↗
PubMed1988

Close linkage of a highly polymorphic marker (D5S37) to familial adenomatous polyposis (FAP) and confirmation of FAP localization on chromosome 5q21-q22.

Fifteen apparently unrelated Dutch families with familial adenomatous polyposis (FAP) also known as familial polyposis coli (FPC; McKusick No. 17510) were screened for linkage with the DNA probe C11p11 localized on chromosome 5q21-22 and previously reported to be closely linked to FAP (Bodmer et al. 1987; Leppert et al. 1987). In our study C11p11 was minimally informative, which is ascribable to its low heterozygosity in the North European populations. Of the above families, 12 were investigated also for linkage with D5S37 (DNA probe Pi227). Data from 11 of them were found to be informative and showed that FAP is closely linked to D5S37 previously localized on chromosome 5q21 (peak lod score 7.85 at a recombination fraction of 0.048 with 95% probability limits 0.005-0.145). Results discussed below indicate for the first time that the most likely location of the FAP gene is in the band 5q22 very close to 5q21, if not in the transitional zone between these two bands. The probe Pi227 recognizes 4 restriction fragment length polymorphism (RFLP) sites, exhibiting a total of 9 alleles with 24 theoretically possible haplotypes in the Dutch population. Therefore, this probe appears to have potential as a generally useful predictive marker for FAP until much closer and similarly useful markers become available.

Adenomatous Polyposis Coli↗
PubMed1987

Plasminogen activators and tumor development in the human colon: activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas.

Malignant changes are often accompanied by alterations in activity and composition of the plasminogen activators (PA). To study the relationship between PA expression and the development of colorectal cancer, we determined urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) activity in normal mucosa (n = 80), adenomatous polyps (n = 76), and adenocarcinomas (n = 71) of the colon. Tissues obtained from surgical resection or polypectomy were analyzed for t-PA and u-PA activity in a specific enzymatic assay using plasminogen, a chromogenic substrate, and selective quenching with monospecific antibodies to both activators. The plasminogen activator activities were found to be changed in adenocarcinomas as compared to normal mucosa. The relative contribution of u-PA (expressed as percentage of u-PA) was raised from 6 to 50% for, respectively, normal mucosa and adenocarcinoma. This change could be attributed to a 3-fold decrease in t-PA activity and a 5-fold increase in u-PA activity in the carcinomas. Adenomatous polyps as a group showed percentages of u-PA [20.2 +/- 1.3 (SE)] which were intermediate as well as significantly different (P less than 0.001) from those of normal mucosa and adenocarcinomas. This observation was strengthened by a gradual rise in the relative contribution of u-PA in four resection specimens containing both adenomatous polyps and adenocarcinomas. Zymography showed the presence of minor quantities of PA-PA inhibitor complexes in the tissue extracts studied. The present study shows that the sequence of normal mucosa-adenomatous polyp-adenocarcinoma in the colon is associated with a parallel change in plasminogen activator activity. Thus, change in the regulation of plasminogen activator activity is an early event in the development of colorectal cancer.

Adenocarcinoma↗
PubMed1987

HLA antigens in colorectal tumours--low expression of HLA class I antigens in mucinous colorectal carcinomas.

Expression of HLA antigens and beta 2-microglobulin was studied by immunoperoxidase staining of frozen sections of 9 mucinous and 10 nonmucinous colorectal adenocarcinomas, 1 cloacogenic carcinoma, 12 colorectal adenomas and 4 samples of normal colorectal mucosa using monoclonal antibodies (MAbs). Staining results were related to histopathological features. HLA Class I antigens were strongly expressed in morphologically normal colorectal epithelium, in all adenomas tested and in all non-mucinous carcinomas. In contrast, expression of HLA class I antigens by the majority of tumour cells was present in only 2 of the 9 mucinous carcinomas, whereas 2 of these mucinous carcinomas were completely negative. In the mucinous carcinomas a striking scarcity of mononuclear inflammatory infiltrate, especially around the mucus accumulations, was observed. HLA class II antigen expression was not detected in normal epithelium and was only focally present in 1 of the 12 adenomas. In 6 out of the 20 carcinomas tested between 20% and 90% of the tumour cells were stained by MAbs against HLA class II antigens. Apart from the low expression of HLA class I antigens in mucinous carcinomas no relationship was found between expression of HLA antigens and histological features of the tumours. The relative poor prognosis of mucinous colorectal carcinoma as reported in the literature may be associated with low expression of HLA class I antigens and scant mononuclear inflammatory infiltrate, which may be a reflection of a weak immune response to the tumour cells.

Adenocarcinoma↗
PubMed1987

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy.

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.

Female↗