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B S Carter

Publications and source records attributed to B S Carter.

At least 19 recordsLinked to original sources
PubMed1992

Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer.

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.

Cadherins↗
PubMed1992

Androgen receptor gene mutations in human prostate cancer.

We screened human prostate cancer tissues for the presence of somatic mutations in the hormone binding domain of the androgen receptor (AR) gene. Exons E-H were amplified from genomic DNA using the polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE), which separates DNA fragments that differ by only a single base. We detected a mutation in exon E of the hormone binding domain in 1 of 26 specimens of untreated organ-confined stage B prostate cancer. The mutation was not detectable in peripheral blood lymphocyte DNA. Lymphocyte DNA (wild-type AR) migrated in DGGE as a single band. The tumor DNA migrated in DGGE as four bands, consistent with the presence of cells with mutant AR plus cells with wild-type AR and indicating that the tumor contained a somatic mutation. To our knowledge, a somatic AR gene mutation has not been reported previously. Sequencing revealed a G----A substitution in codon 730, changing valine to methionine. Codon 730 is in a region highly conserved among all steroid receptors. The abundance of the mutated fragment (about 50% of the DNA in the specimen) indicates its presence in cells with a growth advantage. A somatic mutation could be detected by DGGE if it represented at least 10% of the sample. Failure to detect mutations in other specimens analyzed may be due to this limit of sensitivity, the presence of mutations in other parts of the AR, or a low frequency of mutations in early stage disease.

Amino Acid Sequence↗
PubMed1992

Mendelian inheritance of familial prostate cancer.

Previous studies have demonstrated familial clustering of prostate cancer. To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk of prostate cancer in these families. Furthermore, segregation analyses revealed that this clustering can be best explained by autosomal dominant inheritance of a rare (q = 0.0030) high-risk allele leading to an early onset of prostate cancer. The estimated cumulative risk of prostate cancer for carriers revealed that the allele was highly penetrant: by age 85, 88% of carriers compared to only 5% of noncarriers are projected to be affected with prostate cancer. The best fitting autosomal dominant model further suggested that this inherited form of prostate cancer accounts for a significant proportion of early onset disease but overall is responsible for a small proportion of prostate cancer occurrence (9% by age 85). These data provide evidence that prostate cancer is inherited in Mendelian fashion in a subset of families and provide a foundation for gene mapping studies of heritable prostate cancer. Characterization of genes involved in inherited prostate cancer could provide important insight into the development of this disease in general.

Adult↗
PubMed1992

PROFIS doc.

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Military Medicine↗
PubMed1991

Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles.

Evidence supporting a broad role for the inactivation of the p53 gene in human tumorigenesis has been provided by studies showing that the p53 gene is mutated in many human cancers. In this study, we report on the mutational status of the p53 gene in prostate cancer cells and provide functional evidence that the wild-type p53 gene may have a role in suppressing prostatic tumorigenesis. Sequence analysis of exons 5-8 of the p53 gene reveals that three of five prostate cancer cell lines (TSUPr-1, PC3, DU145) contain mutations which alter the amino acid sequence of this most highly conserved portion of the gene. One of two primary prostatic cancer specimens examined also contained a mutation in this region. Transfection of the wild-type p53 gene versus a mutated p53 gene into two cell lines with p53 mutations results in reduced colony formation. Wild-type p53 gene expression is apparently incompatible with continued growth of these tumor cells inasmuch as none of the colonies which formed after wild-type transfections retain the transfected p53 sequences. Immunocytochemical data indicate that prostate carcinoma cells expressing the transfected wild-type p53 gene are growth arrested because they exhibit a reduced level of thymidine incorporation into DNA. This study is the first report of p53 gene mutations in prostate cancer cells and suggests a functional role for the p53 gene in suppressing prostatic tumorigenesis.

Alleles↗
PubMed1991

Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles.

The influence of preservation or excision of the neurovascular bundles on return of sexual function is analyzed. Between 1982 and 1988, 600 men 34 to 72 years old underwent radical retropubic prostatectomy for prostate cancer. Of the 503 patients who were potent preoperatively and followed for a minimum of 18 months 342 (68%) are potent postoperatively. Three factors were identified that correlated with the return of sexual function: 1) age, 2) clinical and pathological stage, and 3) surgical technique (preservation or excision of the neurovascular bundle). In men less than 50 years old potency was similar in patients who had both neurovascular bundles preserved (90%) and patients who had 1 neurovascular bundle widely excised (91%). With advancing age of more than 50 years sexual function was better in patients in whom both neurovascular bundles were preserved than in patients in whom 1 neurovascular bundle was excised (p less than 0.05). When the relative risk of postoperative impotence was adjusted for age the risk of postoperative impotence was 2-fold greater if there was capsular penetration or seminal vesicle invasion, or if 1 neurovascular bundle was excised (p less than 0.05). These data indicate that the return of sexual function postoperatively in men more than 50 years old is quantitatively related to preservation of autonomic innervation. In these men when it is necessary to excise the neurovascular bundle on 1 side, consideration in the future should be given to approaches that may restore autonomic function through nerve regeneration, for example partial excision of the bundle or cavernous nerve grafts.

Age Factors↗
PubMed1991

Genetic changes associated with prostate cancer in humans.

We have detected allelic loss in a majority of prostate cancers analysed. These losses have been detected on several chromosomes known to harbour tumour suppressor genes important in the development of other tumour types. Elevated rates of loss of heterozygosity on chromosome 16q and 10q suggest that tumour suppressor genes important in the pathogenesis of prostate cancer may be present on these chromosomes. Conversely, determination of the frequency of ras gene mutations in prostate cancer tissue suggests that these genetic alterations play a minor part in both the initiation and progression of this disease in humans.

Biomarkers, Tumor↗
PubMed1991

Familial risk factors for prostate cancer.

This chapter describes the application of the genetic epidemiological approach to the study of human prostate cancer. We review the evidence for the familial clustering of prostate cancer and the Mendelian nature of this aggregation. The nature of this clustering is such that the closer genetically a man is to an affected relative and the greater number of relatives affected in a man's family, the greater his risk of prostate cancer. A complex segregation analysis of the 691 prostate cancer families showed that prostate cancer clustering can be explained by Mendelian inheritance of a rare autosomal gene producing prostate cancer at an early age. A model of inherited prostate cancer in the setting of multistep carcinogenesis is presented. The implications of these data for clinicians who diagnose and treat prostate cancer are also discussed.

Aged↗
PubMed1990

ras gene mutations in human prostate cancer.

Point mutations at codons 12, 13, or 61 of the Ha-, Ki-, and N-ras genes are able to convert these normal cellular genes into activated oncogenes. Previous studies have shown that ras gene mutations occur in a variety of human solid tumors and may be important in the pathogenesis of some of these tumors. In order to test the hypothesis that ras gene mutations may be associated with prostate cancer, we have used an oligodeoxynucleotide hybridization assay to detect wild-type and mutant alleles in genomic DNA from prostate tumors and prostate tumor cell lines amplified using the polymerase chain reaction. Twenty-four primary prostate tumors (23 acinar tumors and one ductal tumor) and five prostate tumor cell lines were examined for mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes. Two mutations were detected: an A----G transition causing a glutamine to arginine amino acid substitution at codon 61 of the Ha-ras gene in a primary prostatic duct adenocarcinoma and a G----T transversion causing a glycine to valine amino acid substitution at codon 12 of the Ha-ras gene in a prostate tumor cell line (TSU-PR1) derived from a lymph node metastasis. While the overall frequency of ras gene mutations in prostate tumors is low, when these mutations do occur they may have a role in the progression of disease or the development of the unusual ductal variant of prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1990

Disproportionate septal hypertrophy associated with erythroblastosis fetalis.

We retrospectively reviewed clinical and echocardiographic data on 10 newborns with erythroblastosis fetalis who were admitted to our nurseries between 1984 and 1988 and who required a double-volume exchange transfusion and neonatal intensive care. Echocardiograms were performed in the first 48 hours of life. In 5 patients, disproportionate septal hypertrophy was demonstrated; 1 additional patient had biventricular hypertrophy with a thickened septum but not disproportionate septal hypertrophy. The mean septal: left ventricular free-wall ratio for the group (n = 10) was 1.37. No correlation was apparent between the occurrence of disproportionate septal hypertrophy and newborn glucose, bilirubin, or hematocrit values. When analyzed separately, the 4 patients who did not receive intrauterine blood transfusions had a ratio of 1.73 +/- 0.21 (mean +/- SEM); this was significantly greater than the ratio in the 6 patients who were transfused in utero (1.13 +/- 0.24). In patients who underwent transfusions, there was no correlation between the number of transfusions and the septal:left ventricular ratio. This study reports a significant but previously unrecognized cardiac hypertrophy with disproportionate septal hypertrophy in patients with erythroblastosis fetalis. Our data suggest a sparing effect of intrauterine fetal transfusions. The mechanism by which these transfusions may affect the hypertrophic development of the myocardium remains to be determined.

Cardiomyopathy, Hypertrophic↗
PubMed1990

Epidemiologic evidence regarding predisposing factors to prostate cancer.

In 1990, prostate cancer will be the most common cancer diagnosed in U.S. men and will be the second-leading cause of cancer mortality in these men. One in ten U.S. men will develop prostate cancer in his lifetime. Twenty thousand prostate cancer cases occur each year in men under the age of 65. The average number of years of life lost for a man dying of prostate cancer is nine. In addition, both incidence and mortality of prostate cancer are increasing. A review of the literature regarding prostate cancer is timely in light of recent studies examining possible predisposing factors for this disease. In this review, a framework for understanding genetic and environmental factors which may predispose to prostate cancer is presented. The identification of factors which predispose to clinical prostate cancer offers the possibility of lowering the incidence and mortality of prostate cancer in the United States. Epidemiologic evidence regarding possible predisposing factors to prostate cancer is reviewed.

Causality↗
PubMed1990

Family history and the risk of prostate cancer.

A case-control study was performed to estimate the relative risk of developing prostate cancer for men with a positive family history. Extensive cancer pedigrees were obtained on 691 men with prostate cancer and 640 spouse controls. Fifteen percent of the cases but only 8% of the controls had a father or brother affected with prostate cancer (P less than .001). Men with a father or brother affected were twice as likely to develop prostate cancer as men with no relatives affected. In addition, there was a trend of increasing risk with increasing number of affected family members such that men with two or three first degree relatives affected had a five and 11-fold increased risk of developing prostate cancer. Recognizing that 9-10% of U.S. men will develop prostate cancer in their lifetime, men with a family history of prostate cancer should be advised of their significantly increased prostate cancer risk and should undergo appropriate screening measures for this disease.

Case-Control Studies↗
PubMed1990

Predicting neonatal morbidity after perinatal asphyxia: a scoring system.

Predicting immediate neonatal morbidity after perinatal asphyxia has been difficult. A review of asphyxiated neonates greater than or equal to 36 weeks' gestation admitted to The Children's Hospital Newborn Intensive Care Unit in 1983 was conducted to devise a scoring system that would rapidly predict organ dysfunction observed in the immediate neonatal period. Comparison of potential score components to morbidity by multiple regression analysis yielded significant association with abnormalities in fetal heart rate monitoring, the 5-minute Apgar score, and neonatal base deficit. A scoring system was devised whose sensitivity (93.8%) and specificity (81.3%) were more predictive than any of its individual components. Prospective analysis in a similar population in 1984 validated its ability to distinguish severe from moderate morbidity after asphyxia. Positive predictive value for the score in the combined study groups (n = 98) was 79% and the negative predictive value was 83%. The scoring system may offer a rapid and accurate prediction of organ dysfunction in the immediate neonatal period after asphyxia.

Asphyxia Neonatorum↗
PubMed1990

Allelic loss of chromosomes 16q and 10q in human prostate cancer.

Recent advances in understanding the molecular genetics of common adult tumors have indicated that multiple genetic alterations including the activation of oncogenes and the inactivation of tumor suppressor genes are important in the pathogenesis of these tumors. Loss of heterozygosity is a hallmark of tumor suppressor gene inactivation and has been used to identify chromosomal regions that contain these genes. We have examined allelic loss in the most common tumor in men, prostate cancer. Twenty-eight prostate cancer specimens have been examined for loss of heterozygosity at 11 different chromosomal arms including 3p, 7q, 9q, 10p, 10q, 11p, 13q, 16p, 16q, 17p, and 18q. Fifty-four percent (13/24) of clinically localized tumors and 4 of 4 metastatic tumors showed loss of heterozygosity on at least one chromosome. Chromosomes 16q and 10q exhibited the highest frequency of loss of heterozygosity with 30% of tumors showing loss at these chromosomes. These data demonstrate that allelic loss is a common event in prostate cancer and suggest that chromosomes 16q and 10q may contain the sites of tumor suppressor genes important in the pathogenesis of human prostate cancer.

Alleles↗
PubMed1989

Valproic acid prenatal exposure. Association with lipomyelomeningocele.

Valproic acid is an anticonvulsant that has been associated with open neural tube defects. We report a family in which the maternal use of valproic acid, and other anticonvulsants, during pregnancy resulted in different malformations in two siblings, one of which had a lipomyelomeningocele. The association of valproic acid and closed neural tube defects has not previously been reported. A brief review of the teratogenic effects of valproic acid is included as well as the implications for early surgical management of lipomyelomeningocele.

Abnormalities, Drug-Induced↗