The prognostic value of the monoclonal antibody (D5) detected protein, p29, in primary colorectal carcinoma.
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Colorectal Neoplasms↗
Biomedical subjects
J F Robertson
Publications and source records attributed to J F Robertson.
Objective measurement of therapeutic response in breast cancer using tumour markers.
In 65 patients with systemic breast cancer, a biochemical response index using three tumour markers in combination, carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3) and erythrocyte sedimentation rate (ESR), allowed objective biochemical assessment of response to endocrine therapy. Changes in these three markers at 2, 4 and 6 months showed a highly significant correlation with UICC assessed response at 6 months. At 4 months, changes in these three markers resulted in a selectivity of 93%, with a sensitivity of 92% and a specificity of 82%. Survival of groups of patients assessed biochemically or by UICC criteria for non-progression or progression showed no significant difference. The advantage of the biochemical assessment are that it is objective and reproducible. The assessment gives similar information to the UICC assessment but can be carried out earlier. Changes in the three markers appears to reflect the dynamics of change in tumour mass in response to systemic therapy in contrast to the UICC criteria which reflect structural change.
Adolescent↗
Airborne dust, ammonia, microorganisms, and antigens in pig confinement houses and the respiratory health of exposed farm workers.
This study investigated the environmental conditions on pig farms and the respiratory health of pig farmers and their immunological response to airborne contaminants. Airborne concentrations of dust and ammonia were measured in 20 pig houses; viable microorganisms, endotoxins, and aeroallergens were measured in 6 of these houses, chosen to represent the range in dustiness. The 29 farmers employed on the farms completed a questionnaire and underwent lung function tests; 24 of them provided blood samples for the measurement of specific IgE and IgG antibody to extracts of pig squames and urine, feed components, and bacterial isolates. Mean airborne dust and ammonia concentrations in the pig houses ranged from 1.66 to 21.04 mg/m3 and from 1.50 to 13.23 ppm, respectively. Factors affecting these concentrations include time of year, feed systems used, and levels of ventilation. There was no direct relationship between airborne dust and ammonia concentrations. Airborne microorganisms ranged from 10(5) to more than 10(7) colony-forming units (cfu)/m3; most were bacteria, with few fungi or thermophilic actinomycetes isolated. Gram-positive bacterial genera (Staphylococcus, Micrococcus, and Bacillus spp.) predominated. Concentrations of endotoxin in collected airborne dust were low. Work-related respiratory symptoms, typically chest tightness/wheeze and nasal and eye irritation, were reported by 23 of the 29 workers. Three farmers had specific IgE to pig squames or urine and eight to feed components but none to the microbial extracts. Specific IgG to pig squames or urine and to feed components was demonstrated in 14 and 9 workers, respectively. Specific IgE responses occurred mainly in subjects with chest tightness or wheeze, although specific IgG responses were not related to symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
Agricultural Workers' Diseases↗
Promoting health among the institutionalized elderly.
1. Although health promotion is a current focus of nursing practice, the institutionalized elderly have not been a target of health promotion research by nurses. 2. Health promotion research in nursing home settings by other disciplines has shown that institutionalized elderly benefit from humanistic approaches and that lifestyle enhancement is possible in nursing home settings. 3. Long-term care nurses are in a unique position to empirically investigate the benefits and efficacy of health promotion interventions in institutionalized settings.
Aged↗
An evaluation of differences in prognosis, recurrence patterns and receptor status between invasive lobular and other invasive carcinomas of the breast.
One-hundred-and-seventy-one patients with invasive lobular carcinomas have been matched with 342 patients with non-lobular invasive carcinomas for lymph node stage, tumour differentiation and patient age on a one to two basis. The two groups were investigated for differences in prognostic factors, survival, disease-free interval, metastatic patterns, receptor status, response to endocrine therapy after distant metastases and bilateral cancer rates. Patients with lobular carcinomas survived significantly longer than patients with carcinomas of no specific type, particularly in survival from the time of diagnosis of distant metastases; lobular carcinomas more often responded to endocrine treatment for systemic disease. Lobular cancers had a significantly higher rate of local recurrence, particularly after treatment by excision and breast irradiation. No differences were found between the two groups with respect to regional or distant recurrence rates, distant organ involvement patterns, distant metastatic free intervals and receptor status. Bilateral cancer was more frequent in patients with lobular carcinoma.
Breast Neoplasms↗
What makes long-term-care nursing attractive?
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Adult↗
Zoladex plus tamoxifen versus Zoladex alone in pre- and peri-menopausal metastatic breast cancer.
Phase II studies examining the endocrinological and clinical efficacy of Zoladex and Zoladex plus tamoxifen have been examined in pre- and peri-menopausal women with advanced breast cancer. No adverse endocrinological interaction between the drugs have been observed. Although a higher proportion of static disease was observed with the combination of the drugs, which possibly occurred at the expense of partial remissions, the time to disease progression was extended in women who received Zoladex plus tamoxifen. Remissions were primarily restricted to patients whose tumours were ER positive. Only occasional responses were seen in ER negative disease. This was especially evident where the ER negative tumours were EGF-R positive and showed high rates of cell proliferation.
Adult↗
Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer.
Frozen sections of breast tumor tissue have been stained using an immunoperoxidase [estrogen receptor (ER)-immunocytochemistry] kit incorporating a monoclonal antiserum [H222] to visualize nuclear human ERs. Quantitation of specific staining has been performed by manual procedures using optical microscopy and by a computer-assisted image analysis system (CAS 100). Initial investigations with a test panel of ER-immunocytochemistry-positive tumors revealed a good qualitative agreement between CAS and manual assessments. Reduced variance was, however, observed between quantified ER-immunocytochemistry results from four experienced investigators using the CAS analysis. An extended study confirmed the relationships between CAS and manual methods of assessment. These findings were evident when studies were scored either by assessment of the percentage of positively stained cells (n = 92; r = 0.919; P less than 0.01) or by H-score calculations (n = 92; r = 0.913; P less than 0.01). A good correlation was also found between CAS quantification and the results of an ER enzyme immunoassay of 48 primary breast cancer specimens (r = 0.715; P less than 0.05). In 49 cases it was possible to relate CAS-defined ER status and levels to the subsequent response of patients to endocrine therapy. ER was assessed on specimens obtained prior to commencement of treatments for recurrent breast cancer. Presuming the presence of ER to be a prerequisite for successful therapy, very good correlations between response and both status and levels of positivity were recorded. None of 16 patients with CAS-ER-negative tumors responded to treatment, while 16 of 33 (48.4%) CAS-ER-positive patients achieved an objective response according to International Union Against Cancer criteria. A relationship between response and the degree of CAS-ER positivity was obtained when the CAS score divisions of 0, 1-100, and greater than 100 (response rates, 0, 41, and 64%, respectively) were used. These data demonstrate that automated image analysis offers a reliable, reproducible procedure for quantifying ER in immunocytochemically stained sections. It has potential advantages over manual procedures, providing less opportunity for subjective influences in scoring sections. Future advances in software design should further reduce elements of subjectivity and increase both the speed and reliability of results. We anticipate image analysis becoming a valuable tool in investigations concerning, for example, the influence of heterogeneity of steroid receptor distribution on the rate of recurrence of breast cancer after mastectomy and in the clinical course of the disease.
Breast↗
Detection of polymorphic epithelial mucins in the serum of systemic breast cancer patients using the monoclonal antibody, NCRC-11.
Serum from patients with systemic breast cancer was found to contain elevated levels of polymorphic epithelial mucin (PEM) as detected using an immunoradiometric assay employing the monoclonal antibody NCRC-11. PEM was partially purified from pooled sera from these patients and the complex, polymorphic, high-molecular-mass (greater than 400 kDa) mucin was identified by sodium dodecylsulphate/polyacrylamide gel electrophoresis, Western blotting and immunostaining with the NCRC-11 antibody. Serial serum samples from 16 patients with metastatic breast cancer were assayed for circulating PEM defined by the monoclonal antibody NCRC-11. The clinical course of disease in these patients was assessed independently as progressive, static or responsive. Increasing NCRC-11 antigen levels correlated with disease progression in 6/7 patients, and decreasing antigen levels correlated with an objective response to treatment in 5/6 patients. Measurement of NCRC-11-defined PEM antigen in patients undergoing therapy for metastatic breast cancer showed an overall accuracy of 75%.
Antibodies, Monoclonal↗
Weekly low dosage epirubicin in advanced breast cancer.
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Adult↗
Assessment of four monoclonal antibodies as serum markers in breast cancer.
Four monoclonal-antibody-defined serum markers (CA15-3, HMFG1, HMFG2 and NCRC-11) were examined in five groups of subjects: controls, benign breast disease and stage I/II, stage III and metastatic breast cancer. None of the markers were significantly elevated in primary breast cancer (i.e. stage I/II or stage III) compared with controls or patients with benign breast disease. These markers therefore have no role in screening or in the diagnosis of primary breast cancer. CA15-3, HMFG2 and NCRC-11 were significantly increased in the patients with metastatic breast cancer (P less than 0.001), indicating a potential use in the diagnosis of symptomatic metastases. In patients with metastases, sequential changes in CA15-3 correlated significantly with clinical response to therapy. Thus CA15-3 is a powerful marker of response and in combination with other markers, may provide an objective measurement of response to therapy in patients with advanced breast cancer.
Adult↗
Thymidine kinase in breast cancer.
The enzyme thymidine kinase is associated with DNA synthesis. Thymidine kinase serum levels were studied in normal controls (n = 20), patients with primary breast cancer (n = 60), patients with systemic breast cancer (n = 20) and as a non-cancer disease control group in patients with inflammatory gastrointestinal disorders (n = 20). Comparison of pretreatment values in the cancer patients with the normal controls showed a significant difference between the three groups in relation to stage of disease: mean values 4.22 (+/- 1.08), 6.22 (+/- 2.24) and 9.79 (+/- 7.56) pmol ml-1 h-1 for normal controls, operable breast cancer and systemic breast cancer respectively (P less than 0.005; analysis of variance). Patients with systemic breast cancer had a significantly elevated serum thymidine kinase level compared to controls (P less than 0.01) and patients with primary operable cancer (P less than 0.05). Patients with primary operable cancer had significantly higher serum thymidine kinase levels over normal controls (P less than 0.01). Mean serum TK in patients with inflammatory gastrointestinal diseases was similar to normal controls but significantly less than both patients with primary operable breast cancer and patients with systemic breast cancer. Twenty patients with operable breast cancer were followed up after primary surgery by serial 3-monthly thymidine kinase levels in the disease free interval. Four patients have developed systemic recurrence with a rise in the mean thymidine kinase value to 14.3 pmol ml-1 h-1. Ten patients with advanced breast cancer had serial thymidine kinase levels measured 2-monthly during the first 6 months of primary hormone therapy. The serum values fell in all five responders (mean 9.12-4.78 pmol ml-1 h-1) and rose in all five progressors (mean 8.62-38.5 pmol ml-1 h-1). Serum thymidine kinase reflects stage of disease in breast cancer. Serial thymidine kinase levels in patients with systemic breast cancer reflected response to systemic therapy.
Breast Neoplasms↗
Goserelin (Zoladex) in premenopausal advanced breast cancer: duration of response and survival.
In premenopausal women with advanced breast cancer the luteinising hormone-releasing hormone agonist goserelin (Zoladex, ICI plc) will produce serum levels of oestradiol equivalent to those following surgical oophorectomy or the menopause. This paper reports our further experience of using this drug in 75 premenopausal patients with advanced breast cancer. In addition to response rates, duration of response is reported. An objective response was seen in 25 patients (33%), the median duration of which was in excess of 15 months. Seven patients (9%) showed a complete response to therapy; median duration greater than 37 months. There was no significant difference in time to disease progression (Lee-Desu statistic 18.26, 1 d.f., P = 0.43) and probability of survival (Lee-Desu statistic 3.41, 1 d.f., P = 0.07) between those patients assessed as having either static disease, or those showing a partial response at six months. Response to therapy correlates significantly with the oestrogen receptor status of the primary tumour (X2 = 20.59, 6 d.f., P less than 0.005). The modest side-effects, ease of administration and reversibility make this approach to therapy very attractive. This is to be remembered in that 53% of patients had disease progression whilst receiving goserelin. These patients thus avoided the unnecessary and irreversible morbidity associated with surgical oophorectomy. With the proven efficacy and minimal morbidity associated with goserelin we believe there is no current role for surgical oophorectomy in the management of premenopausal patients with advanced breast cancer.
Adult↗
Carcinoembryonic antigen immunocytochemistry in primary breast cancer.
We studied the immunoreactivity by immunohistology of two carcinoembryonic antigens (CEA) with specific and two CEA antibodies with nonspecific cross-reacting antigen (NCA) cross reactivity (CEA/NCA) in 180 primary breast carcinomas. Positive tissue staining was found in more than 90% of the specimens with CEA/NCA antibodies, compared with less than 30% for both CEA-specific antibodies. There was no correlation between the positivity of CEA immunocytochemistry for any of the four antibodies and histologic grade, lymph node stage, locoregional recurrence, disease-free interval (DFI), or patient survival. This large study with a long follow-up period for patients has shown that CEA and CEA/NCA immunocytochemistry have no relation to prognosis in breast cancer. An extensive review of the literature that confirms these findings should end the controversy over the place of CEA and CEA/NCA immunocytochemistry in breast cancer.
Animals↗
Combined endocrine effects of LHRH agonist (Zoladex) and tamoxifen (Nolvadex) therapy in premenopausal women with breast cancer.
In premenopausal women with breast cancer, the use of the luteinizing hormone releasing hormone agonist, goserelin, results in the production of serum levels of oestradiol equivalent to those after surgical oöphorectomy or in postmenopausal women. The standard first line hormonal treatment for systemic breast cancer in postmenopausal women is tamoxifen. The combination of goserelin and tamoxifen in premenopausal women has been proposed. We have treated 34 premenopausal breast cancer patients with goserelin (3.6 mg) monthly and tamoxifen (20 mg) twice daily: endocrine data are available on all 34 patients. As with goserelin alone, patients on goserelin and tamoxifen showed transient stimulation of serum follicle stimulating hormone over the first 7-10 days with subsequent low gonadotrophin levels. Serum oestradiol and progesterone levels were reduced to castrate levels in all patients studied; no peaks of serum oestradiol were detected. There is no endocrinological contraindication to the use of goserelin and tamoxifen together in premenopausal women with breast cancer either as adjuvant therapy or in treating advanced disease.
Adult↗
An observation of DNA ploidy, histological grade, and immunoreactivity for tumour-related antigens in primary and metastatic breast carcinoma.
A cohort of 36 cases of advanced breast carcinoma were included in the study. DNA ploidy, histological grade, and immunoreactivity for carcino-embryonic antigen (CEA), carcino-embryonic antigen with normal cross-reacting antigen (CEA/NCA), and to NCRC-11 were assessed in primary breast carcinomas and metastases from the ovary and axillary lymph nodes. Changes in these variables between primary tumours and their metastases were found in 44 per cent of cases for DNA ploidy, 44 per cent of cases for histological grade, 17 per cent of cases for immunoreactivity to NCRC-11, 28 per cent of cases for CEA, and 56 per cent of cases for CEA/NCA immunoreactivity, respectively. Alteration of one factor appeared to be independent of changes in other factors. The development of clones with metastatic potential does not appear to be related to consistent changes in any one of the factors examined and suggests that none of these factors would be of prognostic value in advanced breast carcinoma.
Antibodies, Monoclonal↗
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↗
Factors predicting the response of patients with advanced breast cancer to endocrine (Megace) therapy.
We have treated 238 patients with advanced breast cancer with megestrol acetate (Megace, Bristol-Myers): 221 were assessable for response at 6 months by UICC criteria. Thirty-six (16%) patients responded, 54 (25%) were static and 131 (59%) progressed. Survival from the time of starting Megace calculated by log-rank analysis showed no significant difference in survival between patients showing response and static disease at 6 months. Patients with progression of disease within 6 months survived significantly shorter than patients who showed response or static disease at 6 months. Categorizing response at 6 months appeared to identify patients who had static disease of worthwhile duration. ER status of the primary tumour correlated significantly with survival from the time of commencing Megace. However, when Megace was used as a second-line hormone therapy the assessment of response or static disease on prior hormone therapy was a better predictor of the effect of Megace than ER status of the primary tumour.
Adult↗