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Biomedical subjects

M Stower

Publications and source records attributed to M Stower.

10 recordsLinked to original sources
PubMed2000

Allelic imbalance within the E-cadherin gene is an infrequent event in prostate carcinogenesis.

By exploiting two single nucleotide polymorphisms (SNPs) located within the E-cadherin gene, at 16q22, we have determined the frequency of allelic imbalance at this proposed tumor suppressor locus in a series of human prostatic carcinoma DNA samples. Whereas results with seven highly polymorphic microsatellite markers flanking the E-cadherin locus confirmed the existence of three separate loci on chromosome 16, at which allelic imbalance increased with increasing loss of tumor cell differentiation, no allelic imbalance within the E-cadherin gene was detected either by single-strand conformational polymorphism analysis or by direct sequencing. We conclude that the loss of E-cadherin function observed in prostate cancer is not a result of allelic deletion. Genes Chromosomes Cancer 27:104-109, 2000.

Alleles↗
PubMed2000

In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates.

To study the effects of stromal epithelial cell interactions on prostate cancer metastasis, we have used primary human prostatic stromal cells derived from malignant and non-malignant tissues and established epithelial cell lines from normal (PNT1a and PNT2-C2) and tumour (PC-3, DU145 and LNCaP) origins. The effects of stromal cells on epithelial cell growth were studied in direct and indirect (using culture inserts) co-culture and by exposure to stromal cell-conditioned medium (assessed by MTT assay). The influence of stromal cells on epithelial cell invasion was measured using matrigel invasion chambers and on epithelial cell motility using time lapse microscopy. Results indicated that epithelial cell line growth was similarly unaffected or inhibited by stromal cells derived from malignant (n = 8) or non-malignant tissue (n = 8). In contrast, PNT2-C2 and PC-3 cells were found to be the least and the most invasive and motile epithelia respectively. Stromal cultures enhanced the invasion of both epithelial cells, but no differences were observed between the use of malignant and non-malignant tissues. All stromal cultures modestly stimulated PNT2-C2 motility but displayed a greater stimulation of PC-3 cell motility, while stromal cells derived from malignant tissue stimulated PNT2-C2 and PC-3 cell motility more than stromal cultures from non-malignant tissues.

Cell Division↗
PubMed1998

Precise microdissection of human prostate cancers reveals genotypic heterogeneity.

To determine the incidence of genetic heterogeneity in primary prostate cancer, we have microdissected 125 tumor and mesenchymal foci from 18 patient biopsies and analyzed the DNA for loss of heterozygosity using PCR microsatellite markers. In 100% of patients with genetic lesions on chromosome 8p, there was evidence for intratumoral genetic heterogeneity. There was also a low but significant incidence of loss of heterozygosity in mesenchymal tissue. Our results show that phenotypically similar tumor foci can have different genotypes and provide evidence for the multifocality of tumor development in the prostate.

Chromosomes, Human, Pair 8↗
PubMed1997

Analysis of prostate tissue DNA for the presence of human papillomavirus by polymerase chain reaction, cloning, and automated sequencing.

We have analysed the DNA from 24 prostate tissue biopsies, spanning a range of Gleason grading from benign to grade 5 and mixed randomly with cervical cancer samples of known human papillomavirus (HPV) status, for the prevalence of HPV DNA, in a double-blind study to ensure complete objectivity. Polymerase chain reactions (PCR) were performed using general E1 open reading frame primers for HPV under low stringency conditions, in addition to reactions containing primers specific for HPV16, E2, and E6 open reading frames under higher, more stringent PCR conditions. The presence of cellular DNA was verified by the use of primers for hypoxanthine guanine phosphoribosyl transferase. DNA bands were not detected in the prostate biopsies using the HPV16-specific primers under high-stringency PCR conditions, however a predominant band in the 400 bp region was observed in 15 of the prostate biopsies using the general primers and the low annealing temperature of 40 degrees C. This fragment was excised and cloned into the pT7 blue vector and the sequence of the insert determined. Although the cloned sequences initiated and terminated with the two authentic PCR primers, they did not contain a significant HPV-related open reading frame. Our results indicate that HPV type 16 and closely related types, as detected by the general primer pair, are unlikely initiators of prostate carcinogenesis within our population.

Amino Acid Sequence↗
PubMed1997

Co-ordinated changes in expression of cell adhesion molecules in prostate cancer.

The expressions of E-cadherin, the integrin subunits beta 1, beta 2, beta 3, CD44 and alpha-catenin were studied in parallel by immunohistochemistry in a series of 40 prostate biopsies comprising one normal, 11 benign prostatic hyperplasia (BPH), and 28 prostatic adenocarcinomas. As reported by others, there was a consistent loss of E-cadherin expression with increasing tumour grade and de-differentiation. However, a significant proportion of losses occurred at earlier grades than previously reported. The parallel nature of this study showed, for the first time in human prostate carcinoma, a reciprocal expression pattern of E-cadherin and beta 1 integrin in the higher grades of prostate cancer. A reciprocal expression pattern was also found for E-cadherin and CD44 between moderately and poorly differentiated tumours. alpha-Catenin expression was downregulated only in those cells which had previously lost E-cadherin expression, and beta 2 and beta 3 integrin were rarely expressed in prostate tumours. A loss of expression of the luminal epithelial specific keratins CK8 and CK18 was also observed in advanced stage, poorly differentiated carcinomas.

Adenocarcinoma↗
PubMed1995

A microdissection approach to detect molecular markers during progression of prostate cancer.

To investigate the underlying mechanisms of carcinogenesis, we have developed a technique to determine the frequency of genetic changes in prostatic carcinoma tissue. We have demonstrated that at a ratio of between 1:4 and 1:9 mutant-normal alleles, the signal from a mutant TP53 allele is not apparent after polymerase chain reaction (PCR) amplification and further direct sequencing or single-strand conformation polymorphism (SSCP) analysis. To bypass this problem, which is inherent in the heterogeneity of the prostate tissue and of the tumour, we selected areas of graded prostate tumours (Gleason score) from cryosectioned preparations and microdissected these cells (20-100 cells). After anionic resin removal of proteins, PCR amplification of TP53 gene exons 5/6 and SSCP analysis, an abnormal SSCP band shift was observed in suspected tumour cells, compared with microdissected stromal cells used as an internal control, while (1) a crude preparation of tissue DNA carrying the tumour did not show any abnormality and (2) immunostaining by a set of monoclonal antibodies against TP53 protein remained negative. Nucleotide sequence analysis of the different bands confirmed the presence of a mutation in the TP53 gene exon 6 position 13,336 in an abnormal band for one specimen, while no mutation was detected in the normal SSCP band. By targeting recognised tumour cells we can find DNA mutations which are undetectable using the standard technique of whole-tissue DNA extraction, particularly in a heterogeneous tumour such as carcinoma of the prostate.

Base Sequence↗
PubMed1989

Investigation of haematuria in adults.

Haematuria, whether overt or microscopic has a wide range of causes and patients may present to a variety of clinicians. This article describes the modern approach to the investigation of haematuria and emphasizes the importance of cooperation between physicians and surgeons.

Adult↗
PubMed1986

Patterns of fractures in accidental and non-accidental injury in children: a comparative study.

The incidence and pattern of fractures in children who had been abused were compared with those of fractures sustained by children of similar ages in whom abuse had been excluded. From 1976 to 1982 there were 35 children with fractures resulting from child abuse, and all were aged under 5. Of the 826 children in the control group, seen from January to June 1981, 85% were aged over 5. Abused children were much more likely to have multiple fractures (p less than 0.001) and bruising of the head and neck (p less than 0.001). Fractures of the ribs were common in children who had been abused, and their presence, in the absence of major chest trauma, strongly suggested that abuse was occurring. Injuries to the long bones were invariably spiral or oblique fractures or subperiosteal new bone formation--both "gripping or twisting" injuries. Spiral fracture of the humeral shaft was significantly more common (p less than 0.001) in the group of abused children. Classic metaphyseal chip fractures were uncommon. One child in eight aged under 18 months who sustains a fracture may be a victim of child abuse.

Accidents↗
PubMedDate not supplied

Fracture patterns in Nottingham children.

The incidence and pattern of fractures in children less than or equal to 12 years of age living in Nottingham, England, have been reviewed. The annual incidence rate is 16/1,000 children. Fractures are rare in those less than 18 months of age, and incidence increases with age. The most common cause of fracture was a fall in or around the home; the incidence rate of fractures after road traffic accidents was similar in all age groups. Fractures of the distal radius and ulna accounted for 35.8% of all fractures seen, with hand fractures the second largest group (14.7%). The most common fracture type was a green-stick fracture (51.6%), and 18.5% of fractures were epiphyseal injuries. Epiphyseal injuries in children less than 5 years of age, were uncommon whereas spiral/oblique fractures were more common. Rotational trauma is more likely to cause a spiral or oblique shaft fracture in a younger child and an epiphyseal fracture in an older child.

Accidents, Home↗