[The impact of a premature birth on the family; consequences are experienced even after 19 years]. / Impact van vroeggeboorte op het gezin: ook na 19 jaar ondervinden families nog gevolgen.

OBJECTIVE: A premature birth can cause parental stress, anxiety and uncertainty. This study illustrates the long-term consequences of a preterm birth for family life. DESIGN: Retrospective study by questionnaire. METHOD: Parents of 959 children, who were born in 1983 with a gestational age of less than 32 weeks or a birth weight of less than 1500 grams, were approached when their children turned 19 years old. We investigated various aspects of their family lives by means of a written questionnaire. RESULTS: We received completed questionnaires back from 595 parents (62%). The divorce rate was higher in families with a disabled child (26 vs. 14%). Working mothers (n = 257) and fathers (n = 506) experienced negative consequences in their workplace (36% and 2%, respectively). The risk factor was having a handicapped child. Financial problems were present in 11% of the families during the first year and 4% still experienced financial problems after 19 years; risk factors were a handicap, male gender and a low social-economic status (SES) of the parents. Of the respondents, 26% had observed a decrease in social activities and friends during the first year and 15% felt that family and friends provided insufficient support during this year. After 19 years, 4% of the respondents still experienced a negative influence on their social lives. Risk factors were a handicap, normal birth weight (no dysmaturity), male gender and low SES. 28% of parents expressed that during the first year having a preterm child was emotional challenging or difficult to accept. After 19 years, 3% still expressed an unfavourable effect of the preterm birth. Risk factors were handicap, dysmaturity and male gender. CONCLUSION: A premature birth has a great impact on the family, especially when the child has a handicap.

MIB-1 (KI-67) proliferation index and cyclin-dependent kinase inhibitor p27(Kip1) protein expression in nephroblastoma.

PURPOSE: A number of studies have indicated that the tumor proliferation marker MIB-1 and cell cycle inhibitor p27(Kip1) expression are of prognostic importance in a variety of cancers. The present study was performed to evaluate the prognostic value of these molecules in Wilms' tumors. EXPERIMENTAL DESIGN: MIB-1 and p27(Kip1) expressions were investigated by the means of immunohistochemical analysis of 62 Wilms' tumor. Patients were preoperatively treated by chemotherapeutic agents and had a mean follow-up of 5.7 years. RESULTS: MIB-1 and p27(Kip1) were expressed in normal kidney tissues and in the three main components of Wilms' tumor, i.e., the blastemal, epithelial, and stromal cells. In Wilms' tumors, the percentage of MIB-1-positive cells in the blastema ranged between 0 and 42% (mean, 9.4%) and in the epithelial component between 0 and 53% (mean, 19.9%), with a significant difference (P < 0.01). The percentage of blastemal p27(Kip1)-positive cells ranged between 3 and 85% (mean, 55.1%) and for the epithelial component between 1 and 87% (mean, 59%). There was a significant inverse relationship between blastemal MIB-1 and p27(Kip1) expression in Wilms' tumor. Univariate analysis showed that blastemal MIB-1 and p27(Kip1) expression were indicative for clinical progression and tumor-specific survival. In a multivariate analysis, blastemal MIB-1 and p27(Kip1) protein expression proved to be an independent prognostic for clinical progression besides stage. CONCLUSIONS: It was concluded that both MIB-1-based proliferative activity and p27(Kip1) protein expression in the blastema have prognostic impact in Wilms' tumor.

Androgen-independent expression of adrenomedullin and peptidylglycine alpha-amidating monooxygenase in human prostatic carcinoma.

Most of the locally advanced and metastatic prostate carcinomas (PCs) treated with antiandrogenic therapy eventually become refractory to this treatment. Locally produced factors may control prostate tumor biology after androgen withdrawal. Adrenomedullin (AM) is expressed in the prostate and could control cell growth in androgen-independent conditions. AM needs to be amidated by the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to become fully active. The objective of the present study was to analyze whether the expression of preproadrenomedullin (preproAM) and PAM in PC is regulated by androgens. For this purpose, human in vitro and in vivo PC models were grown in the presence or absence of androgens, and the expression of AM and PAM was examined by immunohistochemistry, Western blotting, RT-PCR, and Northern blotting. Furthermore, immunohistochemical analysis of AM in clinical specimens was performed to test if its expression is related to Gleason score and antiandrogenic therapy. In PC cell lines and xenografts, mRNA and protein AM levels were similar in the presence or absence of androgens. PAM expression seemed to be induced by androgen-withdrawal. Our results in clinical samples showed no relationship between AM expression and Gleason score or antiandrogenic treatment. In conclusion, our results demonstrate that preproAM and PAM expression in the human prostate is androgen-independent. In addition, we also report for the first time the expression of a novel PAM transcript in PC, which has not been previously described in other tissues.

Expression and prognostic value Of CD44 isoforms in nephroblastoma (Wilms tumor).

PURPOSE: CD44 is a group of transmembranous glycoproteins formed by alternative splicing of a single messenger RNA. An abnormal pattern of CD44 expression has been demonstrated in several human malignancies. We evaluate the prognostic value of standard CD44 (CD44s) and some of its isoforms in treating clinical Wilms tumor. MATERIALS AND METHODS: The immunohistochemical expression of CD44 isoforms was studied in paraffin material of 61 clinical Wilms tumors. Patients were treated preoperatively with chemotherapy and mean followup was 5.7 years. RESULTS: Generally CD44s, CD44v5 and CD44v10 were expressed in normal kidney tissues and at variable levels in the 3 cell types of Wilms tumor (blastemal, epithelial and stromal). No CD44v6 expression was found neither in normal kidney or in tumor tissue. CD44s, CD44v5 and CD44v10 epithelial expression gradually decreased from stage T1 to T3. By contrast the percentage of CD44 positive cells in the blastemal component significantly increased from T1 to T3. CD44 immunoreactive blastema cells were found in 62%, 44% and 41% for CD44s, CD44v5 and CD44v10, respectively. Blastemal expression of CD44s and CD44v5 statistically significantly correlated with clinicopathological stage. Univariate and multivariate analyses showed that blastemal CD44v5 expression was indicative of poor prognosis. CONCLUSIONS: Increased expression of CD44v5 in the blastemal part of Wilms tumor correlated with tumor stage, clinical progression and tumor related death. Therefore, blastemal CD44v5 expression may be of value in identifying patients with a high propensity for distant metastases. These patients might benefit from adjuvant chemotherapy and/or radiotherapy.

Different profiles of neuroendocrine cell differentiation evolve in the PC-310 human prostate cancer model during long-term androgen deprivation.

BACKGROUND: Neuroendocrine (NE) cells are androgen-independent cells and secrete growth-modulating peptide hormones via a regulated secretory pathway (RSP). We studied NE differentiation after long-term androgen withdrawal in the androgen-dependent human prostate cancer xenograft PC-310. METHODS: Tumor-bearing nude mice were killed at 0, 2, 5, 7, 14, 21, 47, 84, and 154 days after castration. The half-life of the PC-310 tumor was 10 days, with a stable residual tumor volume of 30--40% after 21 days and longer periods of androgen deprivation. RESULTS: Proliferative activity and prostate-specific antigen serum levels decreased to zero after castration, whereas cell-cycle arrest was manifested by increased p27(kip1) expression. A temporary downregulation of androgen receptor (AR) expression was noted after androgen deprivation. The expression of chromogranin A, secretogranin III, and secretogranin V (7B2) increased 5 days after castration and later. Subsequently, pro-hormone convertase 1 and peptidyl alpha--amidating monooxygenase as well as vascular endothelial growth factor were expressed from 7 days after castration on. Finally, such growth factors as gastrin-releasing peptide and serotonin were expressed in a small part of the NE cells 21 days after castration, but strong expression was induced late during androgen deprivation, that is, 84 and 154 days after castration, respectively. CONCLUSIONS: Androgen deprivation of the NE-differentiated PC-310 model induced the formation of NE-differentiated AR(minus sign) and non-NE AR(+) tumor residues. The NE-differentiated cells actively produced growth factors via an RSP that may lead to hormone-refractory disease. The dormant non-NE AR(+) tumor cells were shown to remain androgen sensitive even after long-term androgen deprivation. In the PC-310 xenograft, time-dependent NE differentiation and subsequent maturation were induced after androgen depletion. The androgen-dependent PC-310 xenograft model constitutes an excellent model for studying the role of NE cells in the progression of clinical prostate cancer.