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M van Vliet

Publications and source records attributed to M van Vliet.

At least 19 recordsLinked to original sources
PubMed2004

Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas.

The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF-alpha and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)45. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-alpha/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K(PS)) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K(PS) and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K(PS) post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.

Albumins↗
PubMed2001

A partial BRCA1 sequence homology mapping to 4q28.

Using a BRCA1 cDNA probe in Southern analysis, we detected a sequence of 348 bp on 4q28 that is homologous to the 3' end of BRCA1. A 28-kb sequence contig has been assembled spanning the homologous region, which we designated BRCA1-h. An open reading frame was identified encoding a sequence of 82 amino acids; 22 of the last 23 amino acids are identical to the last 23 residues of BRCA1. BLAST-searches, RT-PCR and RACE-experiments have been unable to provide evidence that BRCA1-h is part of an expressed gene.

Amino Acid Sequence↗
PubMed2000

Genetic analysis of a breast-ovarian cancer family, with 7 cases of colorectal cancer linked to BRCA1, fails to support a role for BRCA1 in colorectal tumorigenesis.

Mutations in the BRCA1 gene cause strongly elevated risks of breast and ovarian cancers but may also confer a 3-fold increased risk for colorectal cancer. To address the relationship between BRCA1 carriership and colorectal tumorigenesis, we studied the genetics of a breast-ovarian cancer family with 7 cases of colorectal cancer. A germline 3938insG mutation in BRCA1 was found in 5 breast-cancer patients, 1 with ductal carcinoma in situ, ovarian cancer and an adenoma of the colon, and in 4/5 colorectal-cancer patients investigated. However, the youngest patient, diagnosed at age 23, was a non-carrier. Loss of the wild-type BRCA1 allele was observed in 3/3 breast tissues (2 breast carcinomas and 1 ductal carcinoma in situ) but in 0/6 colorectal tissues (5 carcinomas and 1 adenoma), suggesting that BRCA1 loss is not critical for colorectal tumorigenesis. To examine the possibility that an as yet unknown gene linked to BRCA1 was involved in the colorectal cancers, chromosome 17 segregation was studied with 7 polymorphic markers encompassing a 20 cM region including BRCA1. None of these markers showed complete allele sharing among all 5 colorectal-cancer patients studied. Clinical history, mutation analysis and microsatellite instability analysis excluded a role for any of the known colorectal-cancer susceptibility genes. In 4 other Dutch families carrying the same BRCA1 mutation, only 1 colorectal-cancer case was reported, of which the carrier status is unknown.

Adult↗
PubMed2000

A sporadic breast tumor with a somatically acquired complex genomic rearrangement in BRCA1.

Germ-line mutations in BRCA1 cause a substantial proportion of inherited breast cancer, and most result in inactivated BRCA1 proteins upon translation. Tumours developing in BRCA1 mutation carriers generally show loss of the wild-type allele. However, acquired inactivating mutations in BRCA1 in non-inherited breast tumours showing loss of heterozygosity at the gene locus have not been detected so far. Here we provide evidence that such mutations can be detected in a small proportion of breast tumours. Prompted by recent reports of Alu-mediated large genomic rearrangements in BRCA1, we have investigated whether such rearrangements might occur in sporadic breast cancer as well and have been missed thus far by traditional PCR-based mutation screening technology. To this end, we performed Southern blot analysis of 81 apparently sporadic breast tumours using probes covering exons 6-24 and 3 restriction enzymes. We identified 1 case with an acquired rearrangement (1.2%), indicating that BRCA1 inactivation through changes in the primary genomic sequence of the gene is uncommon in breast cancer. Genes Chromosomes Cancer 27:295-302, 2000.

Aged↗
PubMed2000

Screening for BRCA2 mutations in 81 Dutch breast-ovarian cancer families.

We have analysed 81 families with a history of breast and/or ovarian cancer for the presence of germline mutations in BRCA2 with a number of different mutation screening techniques. The protein truncation test (PTT) for exons 10 and 11 detected four different frame-shifting mutations in six of these families. Four of the remaining 75 families had given positive linkage evidence for being due to BRCA2. In these families the entire coding region was analysed by single-strand conformational polymorphism, leading to the detection of a non-sense and a splice-site mutation in two of them. While these studies were in progress, Southern analysis of BRCA1 revealed that in our study-population of 81 families, 15 families were segregating either the exon 13 or exon 22 deletion in BRCA1 (Petrij-Bosch et al (1997) Nat Genet 17: 341-345). This prompted us to examine BRCA2 in the remaining 58 families by Southern analysis, using two different restriction enzymes. No aberrations were found in the restriction patterns. Thus, contrary to BRCA1, large genomic rearrangements within the BRCA2 gene do not represent a major mutation mechanism among Dutch breast cancer families.

BRCA2 Protein↗
PubMed1999

Idarubicin overcomes P-glycoprotein-related multidrug resistance: comparison with doxorubicin and daunorubicin in human multiple myeloma cell lines.

The clinical utility of anthracyclines like doxorubicin (DOX) and daunorubicin (DNR) for treatment of multiple myeloma (MM) is limited by the occurrence of multidrug resistance (MDR). Highly lipophilic anthracyclines like idarubicin (IDA) might circumvent MDR and thereby enhance chemotherapeutic efficacy. To determine the efficacy of IDA in myeloma cells, the pharmacokinetics and cytotoxicity of IDA and its major metabolite idarubicinol (IDAol) were compared with those of DNR, DOX, and doxorubicinol (DOXol) in the cell line RPMI 8226-S and two MDR sublines (8226-R7 and 8226-Dox40) that overexpress the drug transporter P-glycoprotein (Pgp). Cytotoxicity assays using MTT (viability) or annexin V (apoptosis) showed a 10-50-fold higher potency of IDA compared with DNR or DOX in the MDR variant cell lines. The difference in cytotoxicity was lower in the sensitive parental cell line (3-fold). These results are explained by a better intracellular uptake of IDA compared to DNR in resistant 8226 cell lines. The Pgp-inhibitor verapamil affected IDA uptake only in the most resistant cell line 8226-Dox40. This indicates that IDA is less sensitive than DNR to transport-mediated MDR. IDAol was at least 32-fold more cytotoxic than DOXol, and more susceptible to Pgp transport than IDA. These studies demonstrate that the efficacy of IDA in MDR MM cell lines is superior to that of DOX or DNR, and that IDA may become an important drug in the treatment of MM, especially in refractory disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Cardiovascular and endocrine responses to experimental stress: effects of mental effort and controllability.

The objective of the study was to investigate the unique and interactive effects of the controllability of a task and mental effort required by that task on cardiovascular and endocrine reactivity, when both were manipulated independently. A 2 x 2 factorial design was used, with two levels of mental effort and two levels of control. Twenty-four healthy male subjects participated in each experimental condition. Heart rate, blood pressure, catecholamine and cortisol responses were determined. High effort lead to greater increases in heart rate, blood pressure and norepinephrine levels. Uncontrollability lead to higher cortisol, blood pressure and norepinephrine responses. In addition, there was an effort x control interaction effect on the diastolic blood pressure response. In conclusion, effort has clear sympathetic effects, whereas control influences both the sympathetic nervous system and the release of cortisol. Having control seems to be most beneficial in high effort situations, at least with respect to sympathetic reactivity.

Adolescent↗
PubMed1997

Specificity of seven monoclonal antibodies against p53 evaluated with Western blotting, immunohistochemistry, confocal laser scanning microscopy, and flow cytometry.

p53 immunostaining of histological sections shows inter- and intratumor variability in distribution and staining intensity which are usually scored semiquantitatively. In order to investigate the variation in p53 expression more accurately and its possible relation to other cellular parameters (e.g., DNA content), we have studied the possibility to measure p53 accumulation by multiparameter flow cytometry. To this end we have evaluated seven, commercially available, monoclonal antibodies (MAbs) against p53 (MAbs 1801, 240, 246, 421, 1620, Do1, and Do7) on five tumor cell lines with known p53 gene status: MCF-7 (wild-type p53 gene), COV362.cl4 and T47d (mutated p53 genes), and SAOS-2 and HL60 (no p53 mRNA). Localization of immunofluorescence was investigated with confocal laser scanning microscopy, immunofluorescence signal intensity with flow cytometry, and antibody specificity with Western blotting. Subsequently, single cell suspensions from two breast carcinomas were flow cytometrically analyzed after triple staining for p53, cytokeratin 8/18, and DNA, and compared to immunohistochemical staining. MAbs Do1 and Do7, and to a lesser extent MAb 421, accurately discriminated p53 positive from p53 negative cell lines. Even at high concentrations these MAbs yielded nuclear immunofluorescence, whereas with MAbs 1801, 240, and 246 strong cytoplasmic signals in both the p53 accumulating and p53 negative cell lines were seen. By using lower antibody concentrations the cytoplasmic immunofluorescence disappeared, but simultaneously the nuclear p53 immunostaining intensity in p53 accumulating cell lines decreased, resulting in false negative nuclei. With MAb 1620 only weak intranuclear spots were obtained in all cell lines tested. Western blotting yielded results with MAbs 1801, Do1, and Do7 in the 53 kD region of the p53 accumulating cell lines. The signal intensity obtained with MAb 1801 was much less compared to MAbs Do1 and Do7. Although all three MAbs are also described as wild-type p53 specific, only MAbs, Do1 and Do7 showed bands in the 53 kD region of cell line MCF-7. With MAb 1801 ascites and MAb 1801 supernatant an additional approximately 80 kD band was present in all cell lines tested, including SAOS-2, indicating cross reactivity of this MAb. Immunohistochemical staining of two clinical breast carcinomas confirmed the results obtained in the cell lines. Multiparameter flow cytometric analysis of these breast carcinomas with MAbs Do1 and Do7 showed intratumor heterogeneity for p53 accumulation, which was independent of DNA index heterogeneity. We conclude that MAbs Do1 and Do7 enable quantitative analysis of p53 accumulation in a multiparameter flow cytometric analysis.

Antibodies, Monoclonal↗
PubMed1997

Three germline mutations in the TP53 gene.

Three germline mutations in the TP53 tumor-suppressor gene are reported, two of which are not reported previously. A missense mutation at codon 265 of TP53 was found in three patients of a family that complied with the definition of the Li-Fraumeni syndrome. A nonsense mutation in codon 306 was found in a woman who had had a rhabdomyosarcoma at age 4 and a subsequent breast cancer at age 22. She was part of a Li-Fraumeni-like family, but the parental origin of the mutation could not be traced. Finally, while screening for somatic alterations in TP53 in a series of 141 sporadic breast tumors, we detected a constitutional missense mutation in codon 235 in a woman diagnosed with breast cancer at age 26 and a recurrence 4 years later. The recurrence, but not the primary tumor, showed an additional missense mutation at codon 245 as well as loss of the wild-type allele. This suggests that the 245 mutation was particularly important for tumor progression and that there might exist heterogeneity in terms of cancer predisposition potential among the various germline TP53 mutations.

Breast Neoplasms↗
PubMed1997

B7-1 (CD80) as target for immunotoxin therapy for Hodgkin's disease.

In this preclinical study, the potential applicability of an anti-B7-1 immunotoxin (IT) for the treatment of Hodgkin's disease (HD) was investigated. Immunohistochemical analysis demonstrated strong expression of B7-1 on Hodgkin and Reed-Sternberg (R-S) cells and clear expression on dendritic cells, macrophages and some B-cells in tissues, but not on other tissue cells. Flow cytometric analysis demonstrated that B7-1 was expressed on a few monocytes, but not on CD34+ cells from bone marrow, resting T- or B-cells from peripheral blood or epithelial and endothelial cell lines. An anti-B7-1 immunotoxin containing the anti-B7-1 monoclonal antibody (MAb) B7-24 and saporin as toxin moiety was constructed and showed an affinity similar to that shown by the native MAb. It exhibited strong cytotoxicity against the B7-1+ B-cell line Raji (IC50 10(-11) M), R-S cell lines HDLM2, KM/H2 and L428 and also against a B7-1-transfected epithelial cell line, A431, whose parental line lacks expression of B7-1. In clonogenic assays with Raji cells or KM/H2 cells, a 3- or 4-log kill, respectively, was observed. No cytotoxicity was found against the B7-1- epithelial and endothelial cell lines or against haematopoietic progenitor cells. In conclusion, an anti-B7-1 immunotoxin was developed that had good cytotoxicity against R-S cell lines and that may be used in the elimination of R-S cells in vivo. A concomitant elimination of activated antigen-presenting cells may avoid development of antitoxin and anti-mouse Ig responses and allow repeated administration.

Antibodies, Monoclonal↗
PubMed1997

BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients.

To date, more than 300 distinct small deletions, insertions and point mutations, mostly leading to premature termination of translation, have been reported in the breast/ovarian-cancer susceptibility gene BRCA1. The elevated frequencies of some mutations in certain ethnic subpopulations are caused by founder effects, rather than by mutation hotspots. Here we report that the currently available mutation spectrum of BRCA1 has been biased by PCR-based mutation-screening methods, such as SSCP, the protein truncation test (PTT) and direct sequencing, using genomic DNA as template. Three large genomic deletions that are not detected by these approaches comprise 36% of all BRCA1 mutations found in Dutch breast-cancer families to date. A 510-bp Alu-mediated deletion comprising exon 22 was found in 8 of 170 breast-cancer families recruited for research purposes and in 6 of 49 probands referred to the Amsterdam Family Cancer Clinic for genetic counselling. In addition, a 3,835-bp Alu-mediated deletion encompassing exon 13 was detected in 4 of 170 research families, while an deletion of approximately 14 kb was detected in a single family [corrected]. Haplotype analyses indicated that each recurrent deletion had a single common ancestor.

BRCA1 Protein↗
PubMed1997

Effect of endurance training and seasonal fluctuation on coagulation and fibrinolysis in young sedentary men.

The effect of 12 wk of submaximal training on hemostatic variables was studied in 20 young sedentary men (Tr) and 19 nontraining matched controls (Con). After training, a more pronounced increase in factor VIII coagulant activity (P < 0.01), reflected in a decrease in activated partial thromboplastin time (P < 0.01) during maximal exercise, was seen. Both basal plasminogen activator inhibitor 1 antigen (PAI-1 Ag) and activity (PAI-1 Act; P < 0.05), as well as basal and exercise-induced tissue-type plasminogen activator antigen (t-PA Ag; P < 0.05), were decreased after training. The overall effect on fibrinolysis was reflected in an increase in the t-PA Act/t-PA Ag ratio in the Tr group. In contrast, during the same period (February-June), the Con group demonstrated an increase in basal PAI-1 Ag and PAI-1 Act (P < 0.05), together with an increase in basal and exercise-induced t-PA Ag (P < 0.05). Both basal and exercise-induced t-PA Act were unchanged, but t-PA Act/t-PA Ag was decreased (P < 0.05) in the Con group. We conclude that physical training promotes both coagulation and fibrinolytic potential during exercise and may reverse unfavorable seasonal effects on fibrinolysis.

Adult↗
PubMed1997

A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families.

We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous.

Adult↗
PubMed1997

Validation of a natural urinary stone data based infrared library searching system with artificial survey samples.

In this study we evaluated a Fourier transform IR spectrometer (Bio-Rad, USA) equipped with a search system for the analysis of urinary stones. We constructed a database of the stone library with the help of results found with X-ray diffraction analysis. In total, we included 223 stone results (213 natural and 10 spurious stones) consisting of single and composite nature. Regarding the latter we used many comparable and many diverging combinations. Applying 60 artificial referee samples that were used in the urinary stone surveys as organized by the German Society for Clinical Chemistry, we found the instrument hit quality index alone, as a measure of best spectral match not entirely sufficient in relation to acceptable performance. This was also caused by the absence of some rare components. Of those 60 survey samples, 17 did not meet the guidelines of the survey organization. These guidelines are: qualitatively correct and quantitatively within tolerance limits +/-20%. Though a number of these samples seemed irrelevant in a clinical setting, they nevertheless represent a challenge for better performance. In the second round, therefore, we included new entries and human expertise as well, which resulted in an upgrading of the score. We only missed, finally, 4 combinations, mainly related to the purine molecule, i.e. uric acid, sodium urate and ammonium urate. In conclusion, based on extension of the library, we consider the search system as acceptable. Despite that, human interpretation proved to be necessary.

Clinical Laboratory Information Systems↗
PubMed1996

The majority of 22 Dutch high-risk breast cancer families are due to either BRCA1 or BRCA2.

We have analyzed, by a combination of mutation and linkage analysis, the genetic basis of 22 breast cancer families in which at least 4 cases of either breast cancer diagnosed under the age of 60 or ovarian cancer had occurred. Chain-terminating mutations in BRCA1 were evidenced in 6 families, and posterior probabilities of > 0.90 of being linked to BRCA1 in 3. The breast versus ovarian cancer ratio in these 9 families was approximately 2:1. Among the remaining 13 families, significant linkage to markers flanking BRCA2 was established in the admixture test with a maximum multipoint lod score of 3.38, but there was no statistical evidence for genetic heterogeneity. The breast:ovarian cancer ratio in these families was 7:1, suggesting BRCA2 confers a much lower risk for ovarian cancer than does BRCA1. These results suggest that BRCA2 will explain a significant proportion of hereditary breast cancer in the Netherlands, and, together with BRCA1, account for the majority of all high-risk families.

BRCA2 Protein↗
PubMed1995

Age at diagnosis as an indicator of eligibility for BRCA1 DNA testing in familial breast cancer.

We searched for criteria that could indicate breast cancer families with a high prior probability of being caused by the breast/ovarian cancer susceptibility locus BRCA1 on chromosome 17. To this end, we performed a linkage study with 59 consecutively collected Dutch breast cancer families, including 16 with at least one case of ovarian cancer. We used an intake cut-off of at least three first-degree relatives with breast and/or ovarian cancer at any age. Significant evidence for linkage was found only among the 13 breast cancer families with a mean age at diagnosis of less than 45 years. An unexpectedly low proportion of the breast-ovarian cancer families were estimated to be linked to BRCA1, which could be due to a founder effect in the Dutch population. Given the expected logistical problems in clinical management now that BRCA1 has been identified, we propose an interim period in which only families with a strong positive family history for early onset breast and/or ovarian cancer will be offered BRCA1 mutation testing.

Adult↗