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K Griffiths

Publications and source records attributed to K Griffiths.

At least 37 records · Page 2Linked to original sources

Potential value of salivary steroids in chronoepidemiological and endocrine-related studies.

Experience from Institute studies has clearly demonstrated the advantages of salivary steroids in clinical endocrinological research and their potential value in chronoepidemiological studies of many kinds that may involve hormones. Of course, the examples and suggestions for areas of research involve many more covariates than those mentioned; but sufficient evidence has been presented to indicate the chronobiological potential of salivary steroid assays in studies of mental health, aggression and behaviour, stress, the endocrine changes occurring from birth to old age and those relating to endocrine cancer. The pioneering studies of Halberg et al (1981) and Haus et al. (1987) have demonstrated the feasibility of carrying out international epidemiological studies as they relate to breast cancer risk and studies of the general population. The potential value of salivary steroid assays in clinical, physiological and epidemiological studies is judged to be considerable.

Chronobiology Phenomena

Endocrine effects of combination antioestrogen and LH-RH agonist therapy in premenopausal patients with advanced breast cancer.

Thirty-eight premenopausal breast cancer patients were treated for periods up to 12 months with a sustained-release formulation of the luteinizing hormone-releasing hormone agonist goserelin [Zoladex, (D-Ser(But)6Azgly10-LH-RH); 3.6 mg depot every 4 weeks] either alone or in combination with the antioestrogen tamoxifen citrate (Nolvadex 40 mg/day). In both treatment groups serum gonadotrophin concentrations fell durig the first month of therapy and were suppressed on continued treatment. In patients treated with the combination therapy FSH concentrations were significantly reduced in comparison with goserelin alone. Relatively normal ovarian activity was observed during the first few weeks of therapy. Thereafter, oestradiol and progesterone concentrations rapidly declined in both treatment groups. Slightly lower serum oestradiol concentrations were recorded in patients receiving combination therapy. No significant adverse side-effects were recorded in either group of patients.

Antineoplastic Combined Chemotherapy Protocols

Ki67 immunostaining in primary breast cancer: pathological and clinical associations.

Ki67 immunostaining has been performed on 136 primary breast cancers and related to various clinical and pathological features of the disease. Staining was most frequently seen in poorly differentiated tumours showing high rates of mitotic activity, but was independent of tumour size, lymph-node status and ER expression. A high level of Ki67 immunostaining was often associated with early recurrence of breast cancer after mastectomy. These data are consistent with the concept of the Ki67 antibody detecting an antigen that is closely related to cell proliferation and thus provides a clinically useful marker for this important characteristic of the tumour.

Adult

Prostatic cancer: aetiology and endocrinology.

Prostate cancer is common in the male population, worldwide. Several therapies are currently available, but only greater understanding of the complex processes that govern the growth of the cancer will produce real progress in treatment.

Humans

Progesterone concentrations in samples of saliva from adolescent girls living in Britain and Thailand, two countries where women are at widely differing risk of breast cancer.

Menstrual-cycle patterns of salivary progesterone concentration were obtained for 131 and 245 adolescent girls up to 4 years postmenarche living in Britain and Thailand respectively. These patterns were graded on a scale of 1 (little or no activity) to 5 (activity similar to that exhibited by the mature premenopausal woman) and the frequency of these grades within groups of girls from each centre was analysed. The major finding was that British girls exhibited a predominance of higher grades of progesterone activity when compared with their Thai counterparts (n = 2 x 58) when matched for chronological and gynaecological ages (P approximately 0.002). This was particularly so for the girls from these two matched groups in the gynaecological age range 2-4 years (P approximately 0.03). The major contribution to this significant difference between the two groups is attributed to the greater effect of chronological age on progesterone secretion in the British girls (P approximately 0.03) compared with the Thai girls (P approximately 0.29). These findings may have implications for facilitating our understanding of the reason for the differing risk of breast cancer in women in both countries.

Adolescent

Immunocytochemical localization of estrogen receptor in human breast tissue.

An immunocytochemical assay for the measurement of estrogen receptor (ER-ICA; Abbott Diagnostics) has been evaluated in 163 human breast carcinomas. Specific binding was observed in the nuclei of 111 of 163 (68%) tumors. An excellent correlation was observed between the ER-ICA and the estrogen receptor enzyme immunoassay. A significant relationship was observed between ER-ICA status and percentage of ER-ICA negative cells, histological grade of malignancy, and mitotic activity of the tumors. A significant correlation was also observed between ER-ICA status and age at mastectomy with 50% of patients with ER-ICA positive breast tumors presenting with their disease over 60 years of age. No association was observed with either tumor size or patient nodal status. Examination of the proportion of negative cells within tumors revealed a trend for the acquisition of poor prognostic features to be associated with an increase in the negative cell population. Data on the recurrence free interval of these patients showed a significant recurrence free advantage in ER-ICA positive patients, particularly those whose tumors contained low numbers of negative cells.

Adult

Genesis of breast cancer is in the premenopause.

In Britain and other high-risk countries, about a third of patients with breast cancer are premenopausal at diagnosis. In the remainder, tumour initiation might have occurred in the premenopause, even though the clinical presentation was late in life. This possibility has important implications for breast cancer prevention and screening. The relations between the patient's age and tumour kinetics, prognosis, oestrogen receptors, and environmental X-ray carcinogenesis were studied, together with the age-related protection afforded by pregnancy. The findings support the hypothesis that breast cancer is initiated in the premenopause.

Adult

Comparison of prostate-specific antigen and prostatic acid phosphatase in the management of prostatic cancer.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostatic cancer. All patients, who participated in a phase III trial (n = 110), had disseminated disease and received first line endocrine treatment of either orchidectomy or a monthly injection of a depot luteinizing hormone-releasing hormone analogue (Zoladex). Serum samples were analyzed for PSA and PAP at 0, 3, 6, and 12 months and patients were clinically assessed at 6 and 12 months. At diagnosis, 72 and 97% of all patients had elevated PAP and PSA concentrations (greater than 4 ng/ml), respectively. Patients with progressive disease had significantly higher PSA and PAP levels at both assessments. A small number of patients in the "complete remission" group had both PSA and PAP levels within the normal range after 3 months of treatment. Similarly, both PSA and PAP levels steadily declined in the group of patients who had partial regression of the disease. The patients with stable disease, however, had a significant rise only in their PSA levels at the 12-month assessment. This data suggest that PSA is more sensitive than PAP in those patients who have a "slow progression" of the disease.

Acid Phosphatase

The use of serum carcinoembryonic antigen to assess therapeutic response in locally advanced and metastatic breast cancer: a prospective study with external review.

Serum carcinoembryonic antigen (CEA) has been measured throughout initial systemic endocrine treatment in 87 patients with stage III and 179 patients with stage IV breast cancer. Clinical response has been assessed after six months according to UICC criteria with external review of clinical and radiological data. Pretreatment CEA concentrations have been compared with those found in 55 'disease free' women attending a diagnostic breast clinic. A strong correlation exists between therapeutic response and alterations in CEA concentration (above 6 ng/ml) in patients presenting with stage IV disease. More than 50% of such patients either present with or develop CEA concentration greater than 6 ng/ml during the first six months of treatment.

Adult

Steroid hormone concentrations in relation to patient prognosis and prostate tumour grade.

Survival of patients who received endocrine therapy as first-line treatment for their prostatic cancer was statistically analysed in relation to several parameters, primary tumour stage, metastatic status, age, pretreatment plasma hormone concentrations and Gleason grade. Prognostic indices were derived for both M0 and M1 patients in which Gleason grade and plasma testosterone concentrations were significant prognostic factors. In the M1 patients growth hormone values were also significant and to a lesser degree age. The relationship of Gleason grade to testosterone, growth hormone, prolactin, the gonadotrophins and age was also analysed. No significant differences in any of these hormones was noted with increasing Gleason grade but the age of patients with Grade 5 tumours was significantly lower.

Carcinoma

Treatment of patients with advanced cancer of the prostate: phase III trial, zoladex against castration; a study of the British Prostate Group.

The interim results of the randomised, Phase III trial of Zoladex against castration in the management of patients with metastatic carcinoma of the prostate is discussed. Trials commenced in October 1984 and incorporated 359 patients when recruitment ceased in January 1986. The preliminary report concerns the first 240 patients who had a minimum of 3 months follow-up. Entry criteria included patients who had no previous treatment with the exception of first-line localised radiotherapy and those who had distant bone or soft tissue metastases. Fourteen patients were excluded on the basis of protocol violations. The objective assessment of response was based on the British Prostate Group Criteria and was performed monthly for the first 3 months and 3-monthly thereafter. Pre-treatment disease characteristics of patients in both groups were similar at entry and there were no significant differences in the subjective response data of patients between the orchidectomy (n = 106) and the Zoladex group (n = 120). Objective response rates at 12 and 24 weeks of treatment were also identical for both treatment groups. Serum testosterone concentrations were below the 'castrate' level (less than 2 nmol/L) for Zoladex group as well as the orchidectomy group up to 48 weeks. The drug was well-tolerated with minimal side effects, those resulting from testosterone withdrawal were similar in both groups. The report therefore indicates clearly that this partical formulation of LH-RH analogue provides a valuable alternative to the surgical procedure in the treatment of carcinoma of the prostate.

Buserelin

The treatment of metastatic prostatic cancer with the slow release LH-RH analogue Zoladex ICI 118630.

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.

Acid Phosphatase