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Biomedical subjects

P Abel

Publications and source records attributed to P Abel.

At least 19 recordsLinked to original sources
PubMed2001

Cyclooxygenase-2: a possible target in schistosoma-associated bladder cancer.

OBJECTIVE: To analyse and compare the expression of cyclooxygenase (COX) enzymes in schistosoma-associated bladder cancer, and to determine any association with tumour grade or stage. MATERIALS AND METHODS: Sixty paired samples of tumour and adjacent nonmalignant urothelium were identified. There were 25 squamous and 28 transitional cell carcinomas, and seven adenocarcinomas. Serial sections were obtained and a standard three-layer immunohistochemistry protocol, using COX-1- and COX-2-specific mouse monoclonal antibodies, applied. RESULTS: COX-1 was expressed mostly in nonvascular smooth muscle with weak reactivity in malignant and nonmalignant urothelium. Nonmalignant urothelium expressed COX-2 weakly, notably in areas of dysplasia and squamous metaplasia whereas there was a significant increase in COX-2 (P < 0.001) with moderate to strong granular cytoplasmic expression in all three malignant histological types. The COX-2 reactivity was higher in transitional and adenocarcinomas than in squamous cell carcinoma (P < 0.001). Areas of carcinoma in situ showed COX-2 reactivity comparable with that in invasive areas and more intense than that detected in dysplastic or metaplastic urothelium (P < 0.001). There was a statistically significant positive correlation between COX-2 expression and tumour grade (P = 0.0052). CONCLUSION: COX-2 is over-expressed in schistosoma-associated bladder cancer, consistent with a potential role for COX-2 inhibitors in the prevention and management of this disease.

Adenocarcinoma↗
PubMed2000

Decreased HLA-A expression in prostate cancer is associated with normal allele dosage in the majority of cases.

A comparison has been made of the phenotypic expression of MHC class I antigens with the corresponding HLA-A genotype in 15 cases of benign prostatic hyperplasia (BPH) and 34 cases of primary locally invasive prostatic carcinoma. Expression of class 1 protein, detected by immunocytochemistry, was partially or completely lost in approximately 90% of the tumours examined. Comparative genomic analysis of the beta2 microglobulin (beta2m) gene and 15 individual HLA-A haplotypes using a polymerase chain reaction (PCR)-based method demonstrated abnormal gene dosage in the minority of cases: homozygous deletion of the beta2m locus was detected in one case and HLA-A allele in two cases (HLA-A1 and HLA-A2, respectively), representing approximately 8% of the population studied. This first comparative study of gene dosage and expression of class 1 protein reported for prostate cancer reveals that deletion is not the cause of the partial or complete loss seen in the majority of cases. This raises the possibility, in the future, for novel selective immunomodulatory therapeutic strategies which stimulate a clinically significant re-expression of class 1 protein and associated cytotoxic T-cell response.

Alleles↗
PubMed2000

Phenotypic and genotypic characterization of commonly used human prostatic cell lines.

OBJECTIVE: To investigate and catalogue systematically the phenotypic and genotypic characteristics of the commonly used prostatic cell lines using immunocytochemistry and polymerase chain reaction (PCR) of hypervariable sequences within the genome to provide a 'fingerprint' characteristic of each cell line. Materials and methods Malignant (LNCaP, LNCaP-r, PC-3, DU-145) and benign immortalized prostatic cell lines (PNT-1A, PNT-1B, BPH-1) were grown on four-well slides, fixed and subjected to indirect streptavidin-biotin immunocytochemistry. Twenty-three antibodies were used in the following groups: cytoskeletal elements: cytokeratins (CK)-5, -7, -8, -14 (two), -16, -18, -19 (three), -20, vimentin and desmin; MUC1 (three); cell adhesion molecules (E-cadherin, alpha-beta-and gamma-catenin); and prostatic associated proteins: prostate specific antigen (PSA), prostatic acid phosphatase (PAP) and androgen receptor (AR). For the PCR, genomic DNA was extracted from the cell lines and from SKOV3 and MCF7 (positive controls). PCR was performed on three variable regions which were then sequenced: AR exon 1 (CAG repeat polymorphism), and two areas of microsatellite instability (MSI): AR exon 8 and hypoxanthine-guanine phosphoribosyl transferase (HPRT) exon 3. RESULTS: All cell lines were CK-8/18 positive and most also expressed CK-7 and -19. Heterogeneous CK-20 expression was detected for the first time in prostatic cell lines. All lines were positive for vimentin and negative for desmin. MUC1 was expressed in one malignant (DU-145) and all immortalized cell lines. E-cadherin expression was low or absent in three lines: PNT1A, 1B and PC-3. Only PC-3 failed to express alpha-catenin; beta- and gamma-catenin were expressed by all lines. PSA, PAP and AR were only expressed by LNCaP and LNCaP-r. On PCR, the CAG repeat lengths in exon 1 of the AR ranged from 19 to 27. Three pairs of cell lines had the same exon 1 CAG repeat length: LNCaP/PC-3 (26 repeats), BPH-1/DU-145 (19 repeats) and PNT1 A/1B (20 repeats). Exon 8 sequences were identical except for LNCaP, which showed a single base mutation, and HPRT exon 3 sequences were all identical. There was no evidence of generalized MSI in any of the cell lines examined. CONCLUSIONS: The cell lines studied fell into three broad groups according to their phenotypic characteristics: (i) prostatic marker positive (LNCaP and LNCaP-r); (ii) high expression of most antigens (DU-145, PC-3 and BPH-1); and (iii) low or absent expression of most antigens (PNT1 A and 1B). Each of the cell lines derived from PC could be identified on the basis of exon 1 and 8 AR sequence variability. DU145 and BPH-1 had identical profiles of the three areas studied, but these cell lines are easily distinguished by their different phenotypic characteristics. PNT1A and 1B had identical genetic and similar phenotypic profiles, which is unsurprising given that they are subclones derived from the same parental line. Even so, these were separable on the basis of CK-19 immunostaining. Using a combination of geno- and phenotypic markers it was possible to derive a 'fingerprint' for each of the cell lines assessed, which will allow meaningful comparison between similar cell lines held in other laboratories.

Cadherins↗
PubMed1999

Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy.

AIM: To investigate the correlation between androgen receptor expression and fibroblast growth factor 8 (FGF8) mRNA levels. METHODS: 39 human prostate cancers and 14 benign prostatic hypertrophy specimens were examined immunohistochemically for androgen receptor expression and by in situ hybridisation and reverse transcription polymerase chain reaction for FGF8 expression. RESULTS: In 39 tumours there was a statistically significant negative correlation between tumour grade and FGF8 expression and a positive correlation between FGF8 and androgen receptor expression. All 14 benign hypertrophy specimens expressed moderate to high levels of FGF8 and androgen receptor. CONCLUSIONS: Loss of FGF8 may be a factor involved in the development of prostatic cancer.

Fibroblast Growth Factor 8↗
PubMed1998

British urological surgery practice: 2. Renal, bladder and testis cancer.

OBJECTIVE: To investigate the management of urological malignancies in the United Kingdom. METHODS: A postal survey of consultant urologists and general surgeons with an interest in urology was conducted to examine current clinical practice in urological malignancies. RESULTS: Completed questionnaires were received from 273 consultant surgeons who saw an estimated total of 13241 new patients with renal, bladder or testis cancer per year; 82% had access to on-site oncology services and in general there was a consensus in the answers given. Most respondents advised active treatment of an asymptomatic primary renal cancer in the presence of metastases and a significant proportion of patients with metastases were not prescribed immunotherapy nor were offered a multidisciplinary approach for their condition. Forty-six per cent of patients with testis cancer received no advice to store sperm before chemotherapy and there were varied opinions as to the need for surgical resection of residual masses after completion of chemotherapy. CONCLUSION: This survey showed minor variations in the management of renal, bladder and testis tumours in the UK. Consensus management guidelines for urological malignancies and a change in the working relationships between urologists and oncologists is required, to improve the outcome of patients with urological malignancy.

Carcinoma, Renal Cell↗
PubMed1997

Impact of surgery for stress incontinence on morbidity: cohort study.

OBJECTIVES: To describe the impact of surgery for stress incontinence on the severity of symptoms, other mental and physical symptoms, and overall health. To describe the incidence of postoperative complications. DESIGN: Prospective cohort study; questionnaires completed by patients before and 3, 6, and 12 months after surgery. Questionnaires completed by surgeons both before and after surgery. SETTING: 18 hospitals in the North Thames region. SUBJECTS: 442 women treated surgically for stress incontinence between January 1993 and June 1994. 367 women returned the 3 month questionnaire; 364 returned the 6 month questionnaire; and 359 returned the 12 month questionnaire. 49 surgeons provided perioperative information on 285 of the 442 women and postoperative information on 278. MAIN OUTCOME MEASURES: Stress incontinence symptom severity index, other urinary symptoms, bowel function, mental health, complications, global measures. RESULTS: Most women (288; 87%) reported an improvement in the severity of their stress incontinence, though only 92 (28%) were cured (continent). These improvements persisted for at least 12 months. The likelihood of improvement was similar regardless of whether urodynamic pressure studies had been conducted before surgery. Following surgery, women were less likely to suffer from urinary frequency, nocturia, postvoid fullness, dysuria, and urgency. While mental health improved for 194 (71%), a quarter of women reported deterioration. Only 37 (10%) were satisfied with postoperative pain control. A third experienced one or more complications while in hospital, most commonly difficulty urinating. This problem affected 1 in 11 women after discharge. A year after surgery two thirds of women reported feeling better (251; 72%), that the outcome met or exceeded their expectations (230; 66%), and that they would recommend the operation to a friend in a similar situation (239; 68%), and that they would recommend the operation to a friend in a similar situation (239; 68%). Surgeons tended to be more optimistic about the effects of surgery; they were satisfied with the outcome in 176 (85%) cases and would again treat 245 (94%) of the women as they had done previously. CONCLUSIONS: Although surgery reduces the severity of stress incontinence it is not as effective as current textbooks suggest. Women considering surgery should be provided with more accurate information on the likelihood of an improvement in symptoms and the occurrence of complications, including postoperative pain. Urgency and urge incontinence should not be considered contraindications to surgery. The need for urodynamic assessment before surgery should be reappraised.

Cohort Studies↗
PubMed1997

British urological surgery practice: 1. Prostate cancer.

OBJECTIVE: To investigate the treatment of prostate cancer in the United Kingdom. METHODS: A postal survey was conducted of consultant urologists and general surgeons with an interest in urology to assess the current patterns of management of patients with prostate cancer in the UK and to determine patterns of clinical practice. RESULTS: Two-hundred and seventy-four replies were analysed. Radical radiotherapy (50%) and radical prostatectomy (29%) were the most favoured treatment options for patients < 70 years old with poorly differentiated T1 disease; for those aged > 70 years, active treatment was favoured by 183 (67%) consultants with radical radiotherapy (37%) and hormonal intervention (29%) the most frequent choices. In well-differentiated T1 disease, active treatment was favoured by 226 (83%) of consultants for patients < 70 years, with radical prostatectomy (44%) the most frequent choice. For patients > 70 years, observational management was preferred by 190 (69%) of consultants. In poorly differentiated T1 prostate cancer, active treatment was favoured by 252 (91%) for patients < 70, with radiotherapy (50%) the most frequent choice and for patients > 70 years, active treatment was favoured by 67% with radical radiotherapy the most common preference being chosen, by 102 (37%). For asymptomatic locally advanced disease, 55% of consultants favoured active treatment, whilst 63% favoured the active treatment of asymptomatic metastatic disease. For patients with symptomatic metastatic disease, GnRH agonist therapy was the treatment of choice of 66% of urologists and was given as monotherapy by 44% or as part of maximal androgen blockade by 22%. In clinical practice, 82% of urologists have close links with oncology, available through joint clinics or on-site referral. However, < 5% of urologists refer patients to an oncologist before the development of hormone refractory disease. At relapse, only 53% of urologists referred their patients to oncologists or palliative-care clinicians. A wide variety of hormonal treatments was offered at relapse; only 24% of urologists treated their patients by antiandrogen withdrawal or introduction, which is currently the most effective second-line hormonal treatment for recurrent prostate cancer. CONCLUSION: There is a wide variation in the clinical management of prostate cancer and we recommend the establishment of standards of practice.

Attitude of Health Personnel↗
PubMed1997

Erythrocyte carbonic anhydrase activity in smokers and in diabetic patients.

Carbonic anhydrase activity was measured in lyzed erythrocytes from smoking and non-smoking young men as well as from diabetic and healthy young women. Enzyme activity was determined by a changing-pH-assay, using a stirred reaction vessel and glass pH electrode. CAA was lower in smokers than in non-smokers. Furthermore, it was lower in diabetics than in nondiabetic controls. We conclude that cigarette smoking as well as diabetes mellitus may reduce erythrocyte carbonic anhydrase activity.

Adult↗
PubMed1997

Human papillomavirus 16 and 18 infection is absent in urinary bladder carcinomas.

OBJECTIVE: The role of human papillomavirus (HPV) in the pathogenesis of bladder neoplasia remains controversial. Studies to date have mainly utilized polymerase chain reaction and DNA blot techniques to detect HPV DNA. The detection rates have varied from 0 to 81%. One of the major limitations of these techniques is that they lack topographic information. We have used a highly sensitive in situ hybridization (ISH) technique which detects single copies of viral genome and provides topographic information for investigation of HPV infection in bladder carcinomas. MATERIALS AND METHODS: Thirty-one samples of formalin-fixed paraffin-embedded bladder carcinomas (4 adenocarcinomas, 5 squamous cell and 22 transitional cell carcinomas) were examined using non-isotopic ISH with biotin-labelled DNA probes of HPV 16 and 18 subtypes. HPV-positive skin and anal carcinoma samples were used as controls. RESULTS AND CONCLUSIONS: No positive signals for HPV 16 or 18 were detected in any of the bladder carcinoma samples. Given the sensitivity of the technique, the result indicates that HPV 16 and 18 are not implicated in the development of bladder neoplasia compared to certain other epithelial malignancies. The possibility that other subtypes of HPV contribute to bladder epithelial carcinogenesis remains to be clarified.

Adenocarcinoma↗
PubMed1996

Second messenger up-regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines, PC-3 and DU-145.

A theoretical pathway of transcriptional regulation of the androgen receptor (AR) gene is via a cAMP response element (CRE) present in its promoter region (-508 to -501). After 20 h of stimulation with 8-bromo-cAMP, AR mRNA was upregulated in LNCaP but not in either PC-3 or DU-145 cell lines. We have demonstrated that the level of CRE binding protein (CREB) was the same in all cell lines and that the putative AR-CRE forms specific and compatible protein interactions with CREB. The ability to regulate AR gene transcription via the second messenger pathway is lost in the PC-3 and DU-145 cell lines. This may be an important primary mechanism of androgen insensitivity in prostate cancer.

Animals↗
PubMed1996

bcl-2: role in epithelial differentiation and oncogenesis.

The precise regulation and maintenance of balance between cell proliferation and cell death in multicellular organisms is critical for tissue homeostasis. bcl-2 initiates a new gene family involved in the regulation of cell death and survival without affecting cell proliferation. Expression of Bcl-2 has been reported in a wide range of hematopoietic cells, nonneoplastic epithelia (both hormone-responsive and nonresponsive), and epithelial malignancies. Although the major group of epithelial cells expressing Bcl-2 protein are in the proliferating zones, expression is not directly related to cell proliferation. Bcl-2 is also associated with stem cells committed to differentiation and morphogenesis. The survival advantage provided by Bcl-2 prolongs the life span of epithelial cells with differentiation potential and allows proliferation, differentiation, and morphogenesis to proceed. The gene expression in hormone-responsive organs may contribute to the sustained life of those terminally differentiated epithelial cells and a decrease in Bcl-2 levels leads to cell death by apoptosis. Overexpression of bcl-2 protects epithelial cells from death, but it is neither able to immortalize normal cells, nor to cause tumorigenic transformation of immortalized epithelial cells. Heterogeneous expression of Bcl-2 in epithelial malignancies suggests that the gene is differentially regulated. Furthermore, its expression in association with precancerous lesions suggests a role in the early stage of tumorigenesis. The effects of Bcl-2 expression on sensitivity of epithelial cells to drug, radiation, and hormone therapies vary depending on the typed of tumor. Expression of Bcl-2 is associated with resistance to hormone therapy and recurrence in prostate carcinomas, whereas in lung and breast carcinomas it is associated with a better prognosis. Studies now being performed should clarify the underlying mechanisms of differential gene regulation in different tissues and show the clinical significance of the expression of bcl-2 and other members of the bcl-2 gene family.

Animals↗
PubMed1994

Establishment and in vivo characterization of multidrug-resistant dunning R3327 rat prostate-carcinoma cell-lines.

We describe the selection of 3 new multidrug-resistant cell lines derived from tumor cells of different metastatic phenotypes within the Dunning R3327 model of rat prostatic carcinoma. Cell lines of weak (AT2) and strong (AT3 and MAT-LyLu) metastatic behavior were cultured in vitro and challenged with doxorubicin at progressively increasing concentrations. Chemosensitivity was determined colorimetrically by release of precipitated formazan pigment (MTT assay). Expression of the multidrug-resistance glycoprotein (P-170) was monitored immunocytochemically and by Western blotting using monoclonal antibody C219. The behavior of the parental and resultant drug-resistant cells was assessed by their growth in syngeneic rats. Doxorubicin challenge of the initially drug-sensitive parental prostatic carcinoma cell lines resulted in the rapid development of multidrug resistance together with simultaneous expression of P-glycoprotein. While lung and lymph-node metastases developed in host animals inoculated with parental AT3 and MAT-LyLu cells, no metastases developed in the multidrug-resistant progeny of these cell lines. This study has shown that Dunning rat prostate-carcinoma cell lines, previously sensitive to different cytotoxic agents, rapidly become multidrug-resistant and express P-glycoprotein following exposure to doxorubicin. Furthermore, development of multidrug resistance is associated with a less aggressive tumor phenotype and loss of metastatic potential. Nevertheless, it is unlikely that the non-metastatic phenotype of Dunning rat prostatic carcinoma cells is solely associated with expression of P-glycoprotein. These new multidrug-resistant cell lines exhibiting an altered behavioral phenotype will provide a valuable model with which to analyze the relationship between expression of P-glycoprotein and the metastatic phenotype of prostatic carcinoma cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Antibody response in rats against non-toxic glucose sensor membranes tested in cell culture.

Several glucose sensors have been developed, but none are commercially available. The most urgent in vivo problem is the drift of glucose sensor output with time, which may be caused by leakage or denaturation of glucose oxidase, and events at the body-sensor interface such as protein coating, encapsulation with cells, toxicity of the device and inflammation. In the present study, a specific immune response against the outer cellulose acetate membrane of a glucose sensor implanted into rats has also been proved. The immune response against polymeric membranes can be confirmed by detection of specific immunoglobulin G antibodies to cellulose acetate, polyurethane and regenerated cellulose after implantation of the respective membrane. The individually different antibody formation against polymers in rats was amplified by one application of complete Freund's adjuvant in combination with the first implantation. The cell culture results using the fibroblast cell line L-929 showed only a minor toxicity of regenerated cellulose, whereas the other polymers had no effect on cell growth and viability. From the results of this study, it is proposed to integrate immunogenicity as a further parameter for evaluation of the biocompatibility and biosafety of materials or medical devices which are provided for implantation.

Animals↗
PubMed1994

Glucose oxidase electrodes: effect of hydrogen peroxide on enzyme activity?

This paper presents a simple procedure to assess the amount of hydrogen peroxide arising in amperometric glucose oxidase sensors. At an external glucose concentration of 30 mmol/l, which represents the linear range of calibration, a hydrogen peroxide concentration of approximately 0.18 mmol/l is generated. Taking into consideration that in medical applications the main range of interest would be within euglycaemia which is between 4 and 9 mmol/l, it is concluded that in the type of glucose electrode investigated, hydrogen peroxide produced during enzymatic glucose measurement does not appreciably damage the enzyme glucose oxidase.

Biosensing Techniques↗