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D J Sutherland

Publications and source records attributed to D J Sutherland.

At least 19 recordsLinked to original sources
PubMed1995

Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer.

Prostate-specific antigen (PSA) is thought to be produced exclusively by prostatic epithelial cells and is currently used as a tumor marker of prostatic adenocarcinoma. We recently found that 30% of breast cancers contain PSA immunoreactivity (IR-PSA). To examine the prognostic value of PSA in female breast cancer, we measured IR-PSA in tumor cytosols of 174 breast cancer patients and classified the breast cancers as either PSA positive or PSA negative based on an IR-PSA cutoff level of 0.03 ng/mg. IR-PSA was present in 27% of the patients. IR-PSA presence was associated with early disease stage, small tumors, and estrogen receptor-positive tumors. We used the Cox proportional hazards regression model to analyze survival of patients in association with PSA status and found that patients with IR-PSA-positive tumors had a reduced risk for relapse and death in univariate analysis (P = 0.02 and 0.06, respectively) and a reduced risk for relapse in multivariate analysis (P = 0.03). Further analysis indicated that the effect of IR-PSA on relapse-free survival was evident in node-positive or estrogen receptor-negative patients. Our study suggests that IR-PSA is an independent favorable prognostic marker for breast cancer and may be used to identify a subgroup of estrogen receptor-negative and/or node-positive patients who have good prognoses.

Adult↗
PubMed1995

Quantification of creatine kinase BB isoenzyme in tumor cytosols and serum with an ultrasensitive time-resolved immunofluorometric technique.

OBJECTIVES: To develop a highly sensitive immunofluorometric procedure for creatine kinase BB isoenzyme and use it to measure CK-BB in tumor cytosolic extracts and serum of cancer patients and healthy volunteers. DESIGN AND METHODS: For assay development, we used two monoclonal antibodies in combination with time-resolved fluorometry and the biotin-avidin system. We measured CK-BB in breast tumor cytosols and studied its association with steroid hormone receptors. We also measured CK-BB in the serum of healthy subjects and patients with prostate cancer. We have examined the molecular weight of CK-BB in serum using high performance liquid chromatography. RESULTS: The evaluation of the method revealed good precision and accuracy. Study of 336 breast tumor cytosols and 9 normal breast cytosols has shown that CK-BB is overexpressed by 95% of breast tumors and that CK-BB is present in its 80 kDa form. A close association between CK-BB and estrogen but not progesterone receptors was found, suggesting that CK-BB overexpression is another marker of estrogen sensitivity of these tumors. Previous studies, using CK-BB radioimmunoassay could not detect CK-BB in the serum of about 50% of healthy subjects. We have assessed CK-BB levels in 80 male volunteers, detected CK-BB in all sera and provided a detailed distribution of values. We further demonstrated that 30% of prostate cancer patients in remission (PSA < 0.4 microgram/L) post radical prostatectomy and 50% of patients with active prostate cancer (PSA > 20 microgram/L) have elevated serum CK-BB levels. The patients with highly elevated CK-BB also had highly elevated serum PSA. We have demonstrated that some patients who have elevated serum CK-BB also have macromolecular CK complexes in their serum with molecular weights of 700 and 350 kDa as well as the 80 kDa CK-BB isoenzyme. Only the latter was recognized by the assay developed. CONCLUSIONS: CK-BB is a marker of estrogen sensitivity in breast cancer; Patients with prostate cancer have elevated CK-BB in their serum; The new highly specific and sensitive assay may be further used to study the role of CK-BB in various malignancies.

Age Factors↗
PubMed1994

Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers.

We have developed 2 new quantitative methods for measuring anti-p53 antibodies in human serum. Using these methods we analyzed 1,392 sera from patients with various malignancies and 230 sera from individuals without malignancy. Highest prevalence of anti-p53 antibodies was associated with ovarian and colon cancers (15%), followed by lung (8%) and breast (5%) cancers. Prevalence in other malignancies was lower (< 4%). In hospitalized patients and apparently healthy individuals, prevalence was very low (< 2 and 1% respectively). Extremely high antibody concentrations (> 10(5) U/L) were found in 5 ovarian, 2 breast, 1 lung and 1 colon cancers. Sequential analysis of 6 positive samples has shown that the p53 antibody test may have potential for patient monitoring. The p53 antibody-positive sera from breast cancer patients were associated with tumors that were steroid hormone receptor-negative (p < 0.002). We propose that the measurement of p53 antibodies is a relatively specific serological test for cancer, which can be performed with easily automatable and quantitative methodologies and may be further exploited for patient monitoring, prognosis, diagnosis and probably screening for selected cancers.

Aged↗
PubMed1994

Detection of prostate-specific antigen immunoreactivity in breast tumors.

Prostate-specific antigen (PSA) is a glycoprotein produced by the epithelial cells of the prostate. PSA is currently used in clinical practice to facilitate diagnosis and monitoring of prostate carcinoma. The prostate is an organ that possesses androgen, estrogen, and progesterone receptors, and in this respect is similar to the breast. We postulated that breast tumors might also have the ability to produce PSA. We performed these studies on a collection of 525 tumor specimens collected for routine biochemical determination of estrogen and progesterone receptors. Using a highly sensitive immunofluorometric procedure, we measured the p53 tumor suppressor gene product and PSA. Twenty nine percent of the breast tumor extracts contained detectable levels of PSA immunoreactivity (> 0.05 microgram/L). The immunoreactive PSA content was associated with estrogen and/or progesterone receptor-positive tumors (P < 0.002). No association was found between PSA immunoreactivity and levels of the p53 tumor suppressor gene product (P = 0.37). High performance liquid chromatography and Western blot analysis revealed that the PSA immunoreactivity in the tumor had a molecular weight of 30 kDa, similar to that of seminal PSA. Immunoreactive PSA-positive tumors were associated with younger women (P = 0.012) and earlier disease stage (P = 0.064). We postulate that PSA immunoreactivity may be an additional marker of steroid hormone receptor-ligand action.

Age Factors↗
PubMed1994

Quantitative analysis of mutant p53 protein in breast tumor cytosols and study of its association with other biochemical prognostic indicators in breast cancer.

Breast tumors are thought to originate, grow, and metastasize in an environment which includes steroid hormone receptors, their cognate steroid ligands, and many gene products which are regulated by steroid hormone receptor-ligand complexes. In this paper we describe highly sensitive and quantitative immunofluorometric procedures for measuring three proteins that are candidate prognostic indicators in breast cancer, namely, the p53 tumor suppressor gene product, carcinoembryonic antigen (CEA), and prostate specific antigen (PSA). These proteins were quantified in over 950 cytosolic tumor extracts along with estrogen and progesterone receptors (ER, PR). Association analysis between all five biochemical parameters revealed strong negative associations between p53 and receptors and strong positive associations between CEA and receptors. Negative associations between p53 and CEA and between CEA and PSA were also found. These associations, not quantitatively studied in previous reports, are related to each other using a hypothetical model. The observed associations may further contribute to the understanding of the biology of breast tumors.

Breast Neoplasms↗
PubMed1994

Immunoreactive prostate-specific antigen levels in female and male breast tumors and its association with steroid hormone receptors and patient age.

Prostate-specific antigen (PSA) is believed to be a highly specific marker for normal or cancerous prostatic tissue. We recently found that immunoreactive PSA (IR-PSA) is present in 30% of breast tumor cytosols (from 525 breast cancer patients). In this paper we analyzed a new series of 750 breast tumor cytosols, obtained from 744 women and six men, for IR-PSA. The positivity rates in the old and new series were very similar (approximately 30%). Combining the two series of breast cancer patients, we examined the associations between IR-PSA and estrogen (ER) or progesterone (PR) receptors, or patient age. We found that IR-PSA positivity rate declines with age. PSA-positive tumors were highly associated with either ER-positive or PR-positive tumors alone. However, analysis in a subset of tumors that combine the two receptors, ER(-)/PR(-), ER(+)/PR(-), ER(-)/PR(+), and ER(+)/PR(+), revealed that IR-PSA was only associated with PR, and no relationship was found between IR-PSA and ER. We speculate that the presence of IR-PSA in breast cancer may be associated with the PR action and that the association between PSA and ER is indirect due to the known association between ER and PR. As five of the six male breast tumors were found negative for IR-PSA, it is suggested that androgen may not be involved in the presence of IR-PSA in breast tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Evidence for bimodal distribution of breast carcinoma ER and PgR values quantitated by enzyme immunoassay.

Breast carcinoma oestrogen receptor (ER) and progesterone receptor (PgR) values obtained by radioligand binding assays have commonly been observed to have approximate log-normal distributions. We examined the distribution of log-transformed receptor values obtained by enzyme immunoassay for 5468 primary breast carcinomas in five Ontario laboratories. In each laboratory, it was found that the frequency histograms for the log transformed receptor values were not unimodal, and generally were suggestive of bimodality. This was not affected by stratification by age or inferred menopausal status (< or = 49, > or = 50 years), and could not be explained by kit characteristics. However, the low point in the distribution varied from 5 to 63 fmol/mg cytosol protein, depending on the receptor, patient age and laboratory. The tendency towards biomodality was more distinct for ER than for PgR. It remains to be determined whether the low points on the frequency histograms have clinical relevance for discriminating between hormone-sensitive and hormone-insensitive tumours.

Adult↗
PubMed1993

The standardization of estrogen receptors.

Tumour estrogen receptor (ER) status may determine the medical treatment of a patient with breast cancer; yet inter-laboratory results can vary markedly, particularly when absolute cut-offs in fmol/mg cytosol protein are used. The use of standardized log units is proposed to permit greater inter-laboratory comparability. We have assessed the biochemical ER values using the dextran-coated charcoal method with three data sets, two quality control (QC) sets for Ontario laboratories and a data set with values for 184 primary breast cancer patients seen at Women's College Hospital (WCH) between 1985 and 1986. The distributions for all the raw data were skewed toward the lower end of the range; a log transformation improved the symmetry of the distributions. There was marked inter-laboratory variation in the QC data, and standardized log units greatly reduced this variability. The WCH data had similar differentiation by tumour size and nodal status with both the raw data and standardized log units. However, standardized log units provided more consistent evidence of an association between ER and immunohistochemical ERICA. The standardized log units provide quantitative receptor values suitable for multi-centre research, for future work with clinical outcomes, and for the daily management of patients.

Breast Neoplasms↗
PubMed1993

Quantification of p53 protein in tumor cell lines, breast tissue extracts and serum with time-resolved immunofluorometry.

We have developed a highly sensitive time-resolved immunofluorometric procedure for quantifying mutant or wild-type, human or murine, p53 protein. The method uses monoclonal PAb240 or PAb421 antibodies for capture and a polyclonal rabbit antibody for detection. The final immunocomplex is quantified with an alkaline phosphatase substrate which, when hydrolyzed by the enzyme, forms highly fluorescent long-lived complexes with Tb(3+)-EDTA. The detection limit is approximately 1 pg of protein per assay. The assay was applied for the quantification of p53 protein in lysates from 23 cell lines and overproducers of mutant protein were identified. Eight hundred cancer patients sera tested negative for the presence of p53. We have also applied the quantitative immunofluorometric procedure for measuring mutant p53 protein in breast tumor extracts specifically prepared for steroid hormone receptor analysis. Sixty-four out of the 264 extracts (24%) were positive for p53. Significant negative correlations between levels of p53 and steroid hormone receptors were found. The proposed analytical methodology simplifies the assessment of p53 status in tumor extracts, has many advantages over immunohistochemical techniques and is proposed as a method of choice for routine clinical use and other investigations involving p53.

Animals↗
PubMed1991

DNA content and estrogen receptors in primary carcinoma of the breast.

DNA content and estrogen-receptor status were studied in 54 consecutive patients with primary breast carcinoma. Estrogen-receptor determinations were performed by immunohistochemical assay on frozen sections with a monoclonal antibody against the estrogen-receptor molecule and by biochemical analysis with a dextran-coated charcoal method. Nuclear DNA content was measured by flow cytometry performed on formalin-fixed, paraffin-embedded sections. Seventy-two percent of tumours were positive for estrogen receptors by immunohistochemical assay and 67% by biochemical assay. Comparison of the qualitative results of immunohistochemical and biochemical estrogen-receptor determinations revealed a strong correlation between the two assays, with agreement in 90% of the cases (p less than 0.001). Regression analysis showed only a weak relationship between the quantitative results of the two assays. DNA analysis was performed in 51 cases, and 54% demonstrated aneuploid stemlines by flow cytometry. An association was demonstrated between aneuploidy and low levels of estrogen receptor. The association was highly significant with the immunohistochemical assay but not with the biochemical assay. The authors' results suggest that immunohistologic determinations of estrogen receptor status may better reflect the biologic features of the tumour cells. However, improved standardization in reporting the results is necessary if the test is to have widespread use.

Aneuploidy↗
PubMed1991

Larvicidal activity of Tagetes minuta (marigold) toward Aedes aegypti.

The steam distilled oils of 3 species of marigold, Tagetes patula, T. erecta and T. minuta, were tested for larvicidal activity toward third instar Aedes aegypti; activity at 10 ppm was demonstrated only for T. minuta. The larvicidal property of the whole oil dispersed in water persisted for at least 9 days. The terpene, ocimenone, which is a part of the whole oil, was found to be larvicidal only at a higher concentration than the whole oil and to lose its activity within 24 h after dispersal in water. These results suggest a potential utilization of oil of T. minuta or its components for the control of Ae. aegypti and other species of mosquitoes.

Aedes↗
PubMed1989

The use of endocrine therapy.

Endocrine therapy is still a mainstay in the treatment of metastatic breast cancer. It has been observed that about one third of women with metastatic breast cancer will respond to endocrine therapy. This response rate is surprisingly consistent for a wide variety of endocrine approaches, with a few exceptions, such as the use of corticosteroids, androgens, or danazol for which the response rate appears lower. Endocrine therapy is, in general, considerably less toxic than single or combination chemotherapy, but toxicities within the endocrine therapies may vary considerably. Thus, the choice and optimal sequencing of endocrine maneuvers relate largely to minimizing toxicity and optimizing total duration of benefit. A number of newer endocrine approaches including the antiestrogens and aminoglutethimide have recently provided a variety of less toxic choices. Even more recently, compounds such as the LHRH agonists and antiandrogens are being tested, although their use remains experimental. Combinations of two or more endocrine therapies or of chemotherapy and endocrine therapy are currently, also a subject of considerable interest. No studies to date, however, have shown a clear advantage to concurrent chemotherapy endocrine combinations or to the use of two or more concurrent hormonal maneuvers, with the possible exception of the combination of prednisolone with tamoxifen or with oophorectomy, which has improved overall survival in two trials.

Adrenalectomy↗
PubMed1988

Gynecologic-obstetric changes after loss of massive excess weight following bariatric surgery.

A clinical study was undertaken to assess gynecologic-obstetric changes in morbidly obese women who lost greater than or equal to 50% of their excess weight with bariatric surgery. The 138 females (109 of reproductive age), age 35 +/- 9 SD yr, weighed 124 +/- 23 kg before surgery and 79 +/- 13 kg after weight loss had stabilized. Menstrual irregularities were present in 40.4% of premenopausal patients preoperatively; after massive weight loss, cycles were abnormal in 4.6% (p less than 0.001). Infertility problems were present preoperatively in 29.3% Of these, nine tried to conceive after weight loss and were successful. During past pregnancies, medical complications were frequent (hypertension 26.7%, pre-eclampsia 12.8%, diabetes 7.0%, and deep vein thrombosis 7.0%). After weight-loss stabilization, these obstetric complications did not occur. Incidence of urinary stress incontinence decreased from 61.2% to 11.6% (p less than 0.001). Gynecologic-obstetric changes tended to normalize after loss of massive body weight.

Adolescent↗
PubMed1988

Susceptibility status of Aedes albopictus to three topically applied adulticides.

The baseline susceptibility of Aedes albopictus (Sabah strain) to malathion was determined. Both laboratory-colonized and field-collected Ae. albopictus at Harris County, TX are resistant to malathion but susceptible to Scourge. The acute toxicity of bendiocarb to Ae. albopictus is confounded by its rapid knockdown and delayed recovery syndrome of poisoning.

Aedes↗
PubMed1986

Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma.

Tamoxifen was evaluated as initial hormone therapy for metastatic breast cancer in 85 premenopausal patients. Tamoxifen responders continued on tamoxifen, while tamoxifen failures and initial responders who later progressed were to receive ovarian ablation next. Of 74 evaluable patients, 5 had complete responses (CR) and 15 had partial responses (PR) while 12 remained stable (ST), giving response rates of 27% (CR + PR) or 43% (CR + PR + ST). Of the 23 patients who initially responded (CR + PR + ST) to tamoxifen but then progressed and received ovarian ablation alone, 15 are assessable. Nine (60%) responded (CR + PR + ST) to ovarian ablation. Sixteen patients who failed tamoxifen had ovarian ablation alone, and of 14 assessable patients 2 had ST while 12 progressed. Thus response to tamoxifen strongly predicted response to ovarian ablation (P = 0.021). Serial follicle stimulating hormone, prolactin, and estradiol levels suggested that tamoxifen does not act by induction of a "medical ovariectomy" or by alteration of prolactin levels in premenopausal patients.

Breast Neoplasms↗