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Biomedical subjects

K Griffiths

Publications and source records attributed to K Griffiths.

At least 19 recordsLinked to original sources

Relationship of proliferating cell nuclear antigen (PCNA) in prostatic carcinomas to various clinical parameters.

Proliferating cell nuclear antigen (PCNA) expression was determined immunohistochemically, using a monoclonal antibody PC10, in 102 prostatic carcinoma samples and in prostate tissue from 21 patients with benign prostatic hyperplasis (BPH). The percentage of cells with stained nuclei ranged from 1% to 58% in the carcinoma specimens and 0% to 10% in the BPH specimens. A semiquantitative scoring system was devised for the degree of PCNA positivity observed in the tumors. Statistical analysis of the PCNA score in relation to the histological grade of the tumors gave a significant positive or negative correlation between these parameters P less than 0.001. No significant correlation between PCNA score was, however, seen with metastatic status, T category (TMN classification) of the primary tumor, or the patient's age at diagnosis. In 65 prostatic cancer patients of known survival, those individuals whose tumors had a PCNA score of +/- (less than 10% of nuclei stained) were compared with those patients whose tumors were either 1+, 2+, or 3+ (greater than 10% of nuclei stained). Life table analysis of the two groups indicated that the patients with the lower PCNA score survived significantly longer than those with the higher PCNA scores, P less than 0.04. Comparison of the Ki-67 expression in frozen sections with the PCNA expression in wax-embedded tissue of 86 prostatic carcinomas was also undertaken. A significant correlation between these two parameters was found, P less than 0.001, although the growth fraction estimated by Ki-67 expression was generally lower than that given by the PCNA scoring system.

Antibodies, Monoclonal

Pathological and clinical associations of Ki-67 defined growth fractions in human prostatic carcinoma.

Estimation of the growth fraction of 153 prostatic carcinoma specimens employing Ki-67 immunostaining was undertaken and its relationship to various clinical parameters investigated. In prostate specimens, the percentage of tumour nuclei expressing Ki-67 antigen was measured and assigned a Ki-67 score. It was observed that high Ki-67 scores were associated with the poorly differentiated tumours, the correlation of this proliferation marker with histological grade was found to be significant (P less than 0.001). No relationship was observed between the Ki-67 score of the primary tumour with either the patient's age or with the primary tumor stage (T category). The metastatic status of the patient at diagnosis and the Ki-67 score of the tumour were correlated (P less than 0.05), higher Ki-67 scores being associated with M1 disease. Life-table analysis of 86 patients who subsequently received androgen withdrawal therapy, was undertaken with reference to the various Ki-67 scores of their primary tumors. A statistically significant difference in survival times was observed in patients whose Ki-67 values were less than 1% (P less than 0.0001) when compared to those patients whose tumours expressed 1% and over Ki-67 positivity, the former having longer survival times. When patients were subdivided according to their metastatic status and similar life-table analyses were carried out, no statistical difference was found between survival times and Ki-67 scores in M0 staged patients. In the M1 population of patients, however, those patients whose tumours were negative for Ki-67 expression had significantly longer survival times than those patients whose tumours exhibited positive Ki-67 staining (P less than 0.01). Comparing M1 staged patients whose prostate tumor cells exhibited less than 1% Ki-67 positive nuclei with M1 staged patients whose prostate tumour cells contained 1% and higher Ki-67 stained nuclei, a significantly longer survival time was found in the former group of patients (P approximately 0.0001).

Adult

A comparison of menstrual cycle profiles of salivary progesterone in British and Thai adolescent girls.

Menstrual-cycle profiles of salivary progesterone concentration, obtained by radioimmunoassay of daily samples collected throughout the cycle, were obtained from Thai (n = 232) and British (n = 130) adolescent girls up to 4 years postmenarche. These profiles were graded from 1 to 5 ranging, respectively from concentrations at the detection limit of the assay to profiles generally observed for the mature premenopausal woman. Contingency table analysis of the grade frequencies for Thai-British pairs of girls matched for chronological age and age at menarche (n = 2 x 90) demonstrated that British girls had more mature cycles (22/90) than Thais (11/90) (P less than 0.05) particularly in the first 2 years postmenarche (P less than 0.01). For these matched pairs of girls there was no evidence to support the view that girls with an early age of menarche develop their profiles more quickly following menarche than those with a late age of menarche, as previously reported and which was thought to be important in the development of breast cancer. The findings of this study also suggest that adolescent girls in Britain develop their menstrual cycle profiles of salivary progesterone more quickly than their Thai counterparts and this may be of value in formulating hypotheses regarding any role that ovarian progesterone secretion may have on subsequent breast cancer risk.

Adolescent

Prostate-specific antigen: problems in analysis.

We have compared an "in-house" Tenovus Institute prostate-specific antigen (PSA) assay with four different commercial kits (ELSA-PSA, IRMA-Count PSA, PROS-CHECK PSA and TANDEM-R PSA) that are available in the UK. There was only good correlation and linear regression parameters between the in-house assay and one of the kit methods. The difference in values for the same sample ranged from 2 to 100-fold. These discrepancies are due, in part, to the specificity of the polyclonal and monoclonal antibodies used in the procedures and the differing "hook effects" caused by the binding capacity of the antibody pairs in the immunometric assays. Discrepancies will, however, result from the differing potencies of the standards used for the calibration curves. This data highlights the urgency for the introduction of an internationally accepted reference standard for PSA.

Antigens, Neoplasm

Steroids and the prostate.

Interelationships between steroid and growth factor regulation of cell proliferation has been examined in two androgen sensitive prostatic cell lines, grown in defined medium. The cell lines used were derived from normal (CAPE) and neoplastic (LNCaP) tissues. The growth of both cell lines was elevated by challenge with serum, androgens and epidermal growth factor (EGF) used as single agents. The effects of androgen in CAPE were small, but significant while the profound effects of these agents on the growth of LNCaP were confirmatory of other studies. Androgens upregulated EGF receptor expression in LNCaP measured by both ligand binding capacity and mRNA analysis. This was not observed in the CAPE cells. Addition of serum (whole or charcoal stripped) suppressed the observed androgenic stimulation of EGF receptor expression in LNCaP. This apparent anomaly is discussed in relation to the growth enhancing properties of serum in these cell lines and in the wider context of normal and neoplastic growth control in the prostate.

Androgens

Representation of spatial structure in reaching to a visual target.

Reaches made without feedback to positions on an object's surface reflect the spatial form of the surface. In Experiment 1, the reaching pattern varied with the stimulus surface's spatial attributes, consistent with a point-by-point perceptual representation of the surface. In Experiment 2, systematic reaching errors were determined solely by target position regardless of surface structure, implying a highly consistent representation of location. In Experiment 3, illusory slant was imparted to a surface by an aniseikonic lens. Individual variations in directly judged slant were reflected in the reaching pattern, implying organization of local perceptual representation of location and global perception of spatial attributes of the stimulus into a coherent structure.

Adult

The long term prognostic significance of oestrogen receptor analysis in early carcinoma of the breast.

The long term prognostic significance of oestrogen receptors was assessed in a prospective study of 767 patients presenting between the years 1975 and 1981 with stage 1 and 2 breast cancer treated by mastectomy with either full axillary dissection or nodal sampling. Oestrogen receptor binding was determined by a dextran coated charcoal method and median follow up was 11 years. Oestrogen receptors were present in 396 (54%) of tumours. Absence of oestrogen receptors was associated with tumours of high histological grade, but there was no relationship between nodal status or tumour size. Oestrogen receptor status did not predict survival for the group as a whole or when stratified by nodal status. In multivariate analysis both nodal status and tumour size were powerful independent prognostic factors, but oestrogen receptors failed to achieve statistical significance.

Analysis of Variance

Comparison of LHRH analogue (Zoladex) with orchiectomy in patients with metastatic prostatic carcinoma.

Between November 1983 and February 1986, 358 patients with previously untreated metastatic prostatic carcinoma entered a multicentre, randomised trial in the United Kingdom and the Republic of Ireland, in which the LHRH analogue Zoladex (ICI Pharmaceuticals PLC), administered subcutaneously every 28 days, was compared with orchiectomy. Both treatments were equally effective in lowering serum testosterone concentrations to within the surgically castrate range and this was accompanied by equivalent subjective and objective response rates and times to treatment failure. At a median follow-up of 2 years there was no difference in overall survival, confirming that Zoladex is an effective medical alternative to orchiectomy in patients with metastatic disease.

Aged

Steroid hormones and the pathogenesis of benign prostatic hyperplasia.

The pathogenesis of benign prostatic hyperplasia (BPH) is still poorly understood: there is, however, general acceptance that the condition is not premalignant and that it has an etiology distinct from that of cancer. Interest now focuses on the biochemistry of the target prostate cells and the propensity of the gland for uncontrolled growth. Dihydrotestosterone (DHT) is the active intracellular androgen formed from testosterone by 5 alpha-reductase. DHT concentrations appear a little higher in BPH tissue than in normal tissue, and there is no doubt that DHT-receptor complex modulates gene expression. Current studies suggest that DHT is essential but not sufficient for proliferation, and that other regulatory factors, including peptide growth factors, are prerequisite. The growth responsiveness of prostate tissue to androgens may be dependent on the balance between epithelial and stromal tissues, with biologic processes in the epithelium indirectly controlled by androgen-dependent mediators of stromal origin.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

World Health Organization Consensus Committee recommendations concerning the diagnosis of BPH.

The expert committees, which met in Paris in June 1991 under the patronage of WHO to establish a consensus concerning BPH, adopted the recommendations summarised in this report. Despite certain criticisms which can be made, these recommendations offer the advantage of simplicity and uniformity, thereby constituting a "universal language". This will facilitate comparison of patients and therapeutic results, both in everyday practice and in the course of clinical trials. These recommendations will be periodically re-evaluated in the light of clinical experience and technological progress.

Clinical Protocols

Relationship of oestrogen-receptor status to survival in breast cancer.

The oestrogen-receptor (E.R.) content of the primary tumour was measured in 133 postmenopausal women with operable breast cancer. 79 (59%) were positive for E.R. and 54 (41%) negative. Curves of life survival show that women with E.R.-positive tumours live longer than those with E.R.-negative tumours.

Aged

Oestrogen receptors and prognosis in early breast cancer.

In a study of the role of oestrogen-receptor analysis in early breast cancer the oestrogen-receptor content of the tumour was estimated in 286 patients undergoing mastectomy. These patients were followed for up to 39 months, and the recurrence of disease was noted in relation to the presence or absence of oestrogen receptor.Recurrence-rates were significantly higher in patients whose tumours did not contain receptors than in those whose tumours did. This same relationship was seen when women with and without axillary metastases were considered separately. The highest rates of recurrence were in women with axillary lymph-node involvement whose tumours lacked oestrogen receptors. Women without axillary-node involvement whose tumours lacked oestrogen receptors showed the same high rate of recurrence as all women with axillary-node involvement. The oestrogen-receptor content of a primary breast cancer appears to be an independent guide to early recurrence of the disease.

Breast Neoplasms

Plasma spermine concentrations of patients with benign and malignant tumours of the breast or prostate.

A radioimmunoassay has been developed for the measurement of plasma spermine concentrations. The sensitivity of the method is 1 pmol spermine/100 microliters plasma and the crossreactivity was 12% with spermidine and 0.18% with putrescine. Plasma spermine levels of patients with benign and malignant tumours of the prostate or breast were measured using this technique. Concentrations were only occasionally elevated in patients with prostatic tumours compared to normal individuals and there was no difference between those men with benign (mean concn. 0.21 +/- 0.14 nmol/ml plasma) or malignant (mean concn. 0.21 +/- 0.11 nmol/ml plasma) tumours. Only 17% of the patients with breast carcinoma had elevated levels of spermine, although there was a significant difference in the concentrations of the breast cancer group of patients compared to normals. No correlation was found between elevated plasma spermine concentrations and tumour grade or presence or spread of metastases in those patients.

Adolescent