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Biomedical subjects

A Koenders

Publications and source records attributed to A Koenders.

10 recordsLinked to original sources
PubMed2004

Pax genes in myogenesis: alternate transcripts add complexity.

Pax3 and Pax7 are powerful myogenic inducers and hence play a critical role in skeletal muscle development and regeneration. In this paper we discuss the role of Pax3 and Pax7 in dorsal patterning of the somite with subsequent determination of myogenic precursor cells for muscle formation within the developing embryo and in adult muscle. Recent evidence of the ability of stem cells to contribute to muscle regeneration in adult tissues, and the role of Pax7 in conversion of multipotent stem cells to the myogenic lineage are also discussed. Several tissue specific Pax7 transcripts that encode isoforms with different DNA binding characteristics and potentially distinct transactivation specificities are identified. The expression of a range of transcripts in the determination of different tissue lineages and distinct cell populations both in the embryo and in the adult indicates an extraordinary level of complexity. A detailed understanding of these molecules and their functions during embryogenesis and adult muscle formation is imperative for future stem cell therapies.

Alternative Splicing↗
PubMed1986

Standardization of steroid receptor assays in human breast cancer--III. Selection of reference material for intra- and inter-laboratory quality control.

A comparison of estrogen and progesterone receptor (ER and PgR, respectively) analyses using minced frozen tissue and lyophilized cytosols of the same samples demonstrated that intra-laboratory variations in assays performed by 13 members of the EORTC Receptor Group are lowest using the lyophilized samples. Inter-laboratory variation in receptor values was on the same order of magnitude for both types of samples (ca 22% for ER and 30% for PgR). There was no correlation between receptor values measured within each laboratory for either ER or PgR in minced tissues compared to lyophilized cytosols, which illustrates that methods of tissue disruption, extraction of receptors, and preparation of cytosol are sources of intra- and inter-laboratory variation. In some laboratories the handling of the tissue was apparently sub-optimal since a slight but significant difference was found in the overall mean concentration of ER in minced tissue compared to lyophilized cytosol samples. It was concluded that lyophilized tissue samples are the material of choice for routine intra- and inter-laboratory quality controls. However, differences in methods of handling tissue to obtain cytosol should not be disregarded since they lead to increased intra-laboratory variation. A difference was demonstrated between use of a common batch of isotope and the different batches concurrently employed in the laboratories, but the differences were not large enough to warrant use of a common batch for routine inter-laboratory comparisons. Differences in methods used to convert cpm to dpm did not appreciably affect the results when counting samples of tritium containing from 30,000 to 105,000 dpm.

Biological Assay↗
PubMed1986

Standardization of steroid receptor assays in human breast cancer--IV. Long-term within- and between-laboratory variation of estrogen and progesterone receptor assays.

One batch of lyophilized calf uterine cytosol was analyzed for estrogen and progesterone receptor (ER and PgR, respectively) content by 12 members of the EORTC Receptor Group on three different occasions over a total study period of 1 yr: One vial was included with each of 20 consecutive batches of routine tumor analyses between December 1983 and May 1984. Two vials were simultaneously assayed between July and August 1984 (within-run variation). One vial was analyzed at the end of 1984 (November-December). The overall mean ER and PgR values did not change systematically over the total study period of 1 yr. Within the various laboratories, the between-run variations of both ER and PgR assays were considerable and differed from one institution to another (7-26%). For both ER and PgR measurements the average within-run (n = 2) and between-run (n = 20) coefficients of variation were similar (8-9% and 16-17%, respectively). Comparison of the results from multiple sequential assays (c.v. = 12.9%) with those from single assays (c.v. = 21.2%) showed that about 60% of the between-laboratory variance in ER could be explained on the basis of the between-run variance. With regard to PgR analysis, however, the between-laboratory variance decreased only 25%. Standardized use of one type of protein assay (Coomassie brilliant blue) and a standard protein solution (human serum albumin) has decreased the between-laboratory variation of the protein analysis results to less than 15%.

Biological Assay↗
PubMed1983

Standardization of steroid receptor assays in human breast cancer--I. Reproducibility of estradiol and progesterone receptor assays.

Four different lyophilized cytosols were analyzed for estrogen and progesterone receptor content by 13 laboratories. Three of the cytosols were assayed on 9 consecutive working days. The fourth cytosol was analyzed 3 times. All laboratories used the same methods of receptor and protein assays. Estradiol and progesterone receptors were measured by Scatchard analysis with centrally provided radioactive ligands and employing charcoal adsorption of free steroid. Protein was assayed by the Bradford technique with the same lots of Coomassie brilliant blue and human serum albumin standard. All participating groups except one produced receptor results (fmol/ml cytosol) with less inter-laboratory variation than in previous trials. Recalculation of the raw data of all participants by a common computer program further reduced this inter-laboratory variation. The discrepancies between the reported and recalculated receptor binding data are discussed. The intra-laboratory variation was sometimes surprisingly high and occurred at random. Single-dose saturation assays showed good agreement with multipoint Scatchard assays for the high receptor-positive samples, while poor agreement was observed for the heat-inactivated, receptor-negative sample. The use of common reagents and methodologies diminished the inter-laboratory variation coefficients of the protein assay to 14-17%; however, the protein estimation still needs to be improved.

Breast Neoplasms↗
PubMed1983

Standardization of steroid receptor assays in human breast cancer--II. Samples with low receptor content.

Four different lyophilized cytosols with low receptor content were assayed for estrogen and progesterone receptors by 13 laboratories in 7 countries. Each sample was analyzed on three different working days. Three laboratories reported unsatisfactory ER results, whereas the other 10 participants were in good agreement. Employing a cut-off limit of 10 fmol/mg cytosol protein, 95% agreement of ER-positivity was achieved for the two samples with the lowest receptor contents (18 and 21 fmol/mg cytosol protein). For estrogen receptor analyses the inter-laboratory coefficients of variation ranged between 15 and 18%. Both the intra- and inter-laboratory variations and the rate of concurrence on receptor status were less satisfactory for the progesterone than for the estrogen receptor analyses. The variation in protein results among the participating 13 laboratories is decreased to 10%. It is concluded that multi-center clinical trials based upon the estrogen receptor status assigned by individual laboratories are feasible.

Animals↗
PubMed1980

Estradiol receptor activity in lyophilized calf uterus and human breast tumor tissue.

Estradiol receptors (ER) were analyzed in lyophilized human breast tumor specimen and in calf uterus tissue by a dextran-coated charcoal method. No decline of ER occurred when lyophilized calf uterus tissue was stored for six to eight months at 0-4 C and for two weeks at room temperature. During storage of lyophilized human breast tumor tissue for several months at 0-4 C and for four weeks at room temperature, no or only a minor decrease of ER binding sites was observed. Therefore, it is recommended to use lyophilized target tissues for intra- as well as interlaboratory quality control studies of steroid receptor measurements.

Animals↗
PubMedDate not supplied

Tamoxifen versus ethinyl estradiol in the treatment of postmenopausal women with advanced breast cancer.

In a randomized study, 63 postmenopausal patients with advanced breast cancer were treated with ethinyl estradiol (EE2) or the antiestrogen tamoxifen to compare the efficacy and side effects of both drugs. EE2 was always given in combination with chlorothiazide to prevent fluid retention. Pretreatment characteristics of the patients of both groups did not differ significantly. Objective remissions were achieved in 31% of the EE2-treated patients and in 33% of the tamoxifen-treated patients. The median duration of remission was 12 months (range, 5-32) for the EE2 group and 11 months (range, 5-26) for the tamoxifen group (P greater than 0.1), and the estimated median survival times from the start of treatment were 31 and 25 months, respectively (P greater than 0.1). The best treatment results in both groups were obtained in patients with estradiol receptor-positive tumors and less advanced disease. After therapy was stopped, objective withdrawal responses were observed in EE2- but not in tamoxifen-treated patients. Two patients receiving EE2 had to discontinue treatment because of drug-related liver function impairment. Both patients had cholelithiasis. Two patients in the tamoxifen-treated group discontinued therapy because of nausea. Deep venous thrombosis occurred in one patient receiving EE2, whereas two patients receiving tamoxifen developed superficial thrombophlebitis. Other side effects in both groups of patients, including initial hypercalcemia, were mild. It is concluded that both treatment regimens, EE2 or tamoxifen, are equally effective with respect to induction and duration of remission in postmenopausal patients with advanced breast cancer. Side effects of EE2 therapy appeared to be more serious than those of tamoxifen treatment.

Adult↗