Biomedical subjects

L Demers

Publications and source records attributed to L Demers.

8 recordsLinked to original sources

PubMed1992

Synchronization of breast cancer cell proliferation in vivo by combined hormonal and polyamine manipulation.

Optimal synchronization of breast cancer cell proliferation by hormonal means may be limited by cellular heterogeneity in sensitivity to the multistep activation of growth following initial hormone binding to the receptor. We hypothesized that induced synchronous growth may be improved by combined manipulation of the polyamine (PA) pathway since we have previously shown that PAs are distal effectors of hormonal action on proliferation in breast cancer. To test our hypothesis, we induced an initial phase of hormone and PA depletion (castration plus administration of the PA synthesis inhibitor alpha-difluoromethylornithine) in rats bearing N-nitrosomethylurea induced mammary tumors. This was followed by transition phase of hormone repletion in the presence of alpha-difluoromethylornithine (to push the cells into the proliferative cascade up to the distal step controlled by PA) and finally a phase of hormone and PA repletion. Simultaneously, groups of rats were subjected to hormone/PA depletion/repletion individually. The effects of these manipulations on the labeling indices (LIs) of glandular, myoepithelial, and nonepithelial cells were estimated by autoradiography. The combined hormone/PA manipulation yielded the highest degree of synchronization with LIs of the glandular and myoepithelial cells being approximately 2-fold over intact control after only 2 or 3 days of combined repletion. In contrast, hormone treatment alone restored the LIs of glandular cells only to control levels and minimally influenced those of myoepithelial cells. PA manipulation alone failed to affect the LIs of any cell type. Although the rate of tumor regrowth was highest with the combination treatment, the absolute tumor volumes did not differ significantly at the end of the repletion phase between the three regimens. These results indicate that combined hormone/PA manipulation provides the best "therapeutic window" (LI/tumor volume) for implementation of kinetically based cytotoxic chemotherapy.

Animals↗

PubMed1992

Role of polyamines in the growth of hormone-responsive and -resistant human breast cancer cells in nude mice.

Recent in vitro data suggest that at least some hormone-independent breast cancer cells exhibit increased polyamine biosynthesis and resistance to antipolyamine therapy. To address this issue under conditions of in vivo growth, we tested the antiproliferative effect of the polyamine synthetic inhibitor alpha-difluoromethyl-ornithine (DFMO) on hormone-dependent (MCF-7) and -independent (MDA-MB-231, BT-20) breast cancer cell lines growing in nude mice. We observed that DFMO significantly inhibited the growth of established tumors to a similar extent in all cell lines, even though tumor regression was only observed with MCF-7 cells. DFMO, while inhibiting E2-supported MCF-7 breast cancer growth, did not inhibit E2-stimulated progesterone receptor synthesis. Cellular levels of polyamines were highest in MCF-7 cells and lowest in the BT-20 cell line. Tumor content of spermidine was similarly suppressed by DFMO treatment in the 3 cell lines, while the spermine level was unaffected. Cellular putrescine levels were suppressed in MCF-7 and BT-20 cells. Administration of DFMO prior to implantation of fragments of MCF-7 or MDA-MB-231 tumors in nude mice significantly inhibited tumor development to a similar extent. The action of DFMO seemed to be predominantly tumoristatic since new tumors develop in some mice upon discontinuation of the drug. We conclude that the hormone-independent breast cancer cell lines tested do not exhibit increased polyamine biosynthesis or resistance to antipolyamine therapy when grown in vivo in nude mice.

Animals↗

PubMed1992

Elevated soluble c-erbB-2 antigen levels in the serum and effusions of a proportion of breast cancer patients.

PURPOSE: An enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of the c-erbB-2 oncogene product was developed and evaluated to determine if soluble c-erbB-2 could be detected in the serum and effusions of cancer patients. PATIENTS AND METHODS: Sera from 208 previously untreated or progressing cancer patients and 69 healthy controls were assayed in a double-antibody sandwich ELISA that used two monoclonal antibodies to the native extracellular domain of the c-erbB-2 receptor. Fisher's exact test was used to analyze the statistical significance of the frequency of elevated serum c-erbB-2 levels. Immunoprecipitation and Western blotting were used to characterize further the c-erbB-2 immunoreactivity in the serum of four breast cancer patients. RESULTS: Sera from 12 of 53 patients (23%) with metastatic or locally advanced breast cancer, zero of 69 controls, one of 31 patients with ovarian cancer (3%), and two of 124 other cancer patients (2%) had soluble c-erbB-2 values greater than or equal to 5 U/mL. The number of breast cancer patients with elevated serum c-erbB-2 levels was significantly greater than that of the control group (P less than .0001), the ovarian cancer group (P less than .03), and the other cancers group (P less than .0001). Also, two of five effusions (40%) from breast cancer patients had an elevated soluble c-erbB-2 antigen level, compared with zero of 17 effusions from patients with benign diseases. Western blotting of four sera from breast cancer patients with elevated serum c-erbB-2 antigen levels produced bands of approximately 105 kD that seemed to correlate in intensity with increasing ELISA serum levels. CONCLUSION: Serum c-erbB-2 levels are elevated in approximately one fourth of patients with locally advanced or metastatic breast cancer.

Adult↗

PubMed1979

Pericardial-fluid complement: normal values.

Reports of low pericardial-fluid complement levels in systemic lupus erythematosus and rheumatoid arthritis have been difficult to interpret, as few data are available to describe complement concentrations in patients without pericardial disease. The authors therefore determined normal values under standardized conditions of collection, storage, and assay. The normal ranges for pericardial-fluid C3, C4, and total hemolytic complement were 35-127 mg/dl, 6.3-23 mg/dl, and 1.9-9.1 CH50 units, respectively. Storage at -20 C resulted in a 50% reduction in values. Hence, storage at -70 C is recommended. As the level of pericardial-fluid total hemolytic complement is normally low, caution is needed in interpreting its apparent reduction in various immunologic diseases.

Complement C3↗

PubMed1976

Peripheral plasma determinations of prostaglandin E in asthmatics.

Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have recently been implicated in the pathophysiology of reversible airway disease. This study attempted to elucidate baseline prostaglandin E (PGE) plasma levels in asthmatics and the change in these levels after stimulation by a beta-adrenergic agent. Fourteen stable, ambulant patients with reversible airway disease and 28 nonatopic control subjects were studied. All had baseline PGE levels performed. The asthmatics were asked to abstain from all medication for 10 hr prior to evaluation. After baseline evaluation consisting of plasma PGE determination, pulmonary function test, blood pressure, and heart rate, 375 mug of aerosolized terbutaline sulfate was administered to 8 of the asthmatics plus 4 of the nonatopic control subjects; the above measurements were repeated at 15, 30, and 60 min after administration. There was a statistically significant difference in baseline plasma PGE levels between the asthmatics (PGE = 432 +/- 81) and the nonatopic control subjects (PGE = 89 +/- 9) (p less than 0.002). Following terbutaline administration, there was no significant change observed in PGE levels in asthmatic or in control individuals (asthmatics: 0 min, 570, 15 min, 513, 30 min, 514, 60 min, 608; normal subjects: 0 min, 138, 15 min, 137, 30 min, 143, 60 min, 214). In summary, we observed a significant difference in baseline PGE levels between asthmatic and nonatopic control persons. No change, however, was noted in PGE levels after beta-adrenergic receptor stimulation. This observation is consistent with the current hypothesis that beta-adrenergic agents act independently of prostaglandins to increase adenyl cyclase and modify bronchiole smooth muscle tone.

Adult↗

PubMed1976

Measurement of plasma prostaglandins during exercise-induced bronchospasm.

Bronchospasm following exercise is a phenomenon which occurs in most patients with reversible airway disease. The pathophysiologic mechanism leading to this bronchoconstriction with exercise has not yet been defined. Recently, prostaglandins have been implicated in the etiology of asthma. The purpose of this investigation was to determine changes in plasma prostaglandins occurring during exercise-induced asthma. Eight ambulant asthmatics were chosen for baseline pulmonary spirometry and peripheral venous blood prostaglandin E and F levels. The asthmatics were then exercised to 80% of their age-predicted maximal heart rate via a multistage branching treadmill protocol. At 5, 15, and 30 min following exercise, pulmonary spirometry was again performed and peripheral venous blood collected at the indicated times. Clinical bronchospasm as characterized by audible wheezing and greater than 15% decrease in FEV1 and MMEFR was obtained in all of the asthmatics. Peripheral PGE and PGF2alpha determinations following this exercise protocol were not altered significantly: (PGE: 0 min, 238; 5 min, 185; 15 min, 248; 30 min, 256 pg/ml); (PGF2alpha: 0 min, 50; 5 min, 24; 15 min, 25; 30 min, 17 pg/ml) (p less than 0.1). In summary, no significant change in peripheral blood prostaglandin E and F2alpha levels as determined by radioimmunoassay was noted at the time of exercise-induced bronchospasm.

Bronchial Spasm↗

PubMed1976

Decreased prevalence of immediate hypersensitivity (atopy) in a cancer population.

It has been suggested that the atopic population has decreased risk of cancer. This investigation examined the cumulative prevalence of atopy in a population with neoplastic disease and compared this with the prevalence of atopy in an age-matched control group and with published estimates of atopy in the general peopulation. Seventy-four patients with neoplastic disease and 86 patients without cancer were evaluated. The subjects were given a standard allergic questionnaire which evaluated them with regard to a history of allergic symptoms, hives, eczema, frequent colds, frequent unexplained rashes, hay fever, and asthma. All were skin tested with a representative group of regionally significant allergens. There was a 15-fold decrease in prevalence of atopy in the cancer population, compared with the control group and compared with published estimates of atopy in the general population.

Adult↗

PubMed1975

Ragged-red fibers. A biochemical and morphological study.

Histochemical, ultrastructural and biochemical studies were performed on muscle biopsy specimens from a 30-year-old man with proximal limb weakness. Modified Gomori trichome stains of anterior tibial muscle revealed accumulations of red-staining material in the subsarcolemmal and intermyofibrillar regions of virtually every fiber (ragged-red fibers); these accumulations were rich in oxidative enzymes. Electron microscopy of this muscle showed that the red-staining areas consisted of large collections of abnormal-appearing mitochondria. Mitochondria isolated from the quadriceps muscle showed lack of respiratory control with alpha-glycerophosphate as substrate. However, the lack of respiratory control with alpha-glycerophosphate must be interpreted with caution since the quadriceps muscle was severely degenerated, and biochemical alterations of mitochondria may occur secondary to muscle degeneration itself. Nevertheless, this is the second reported case of lack of respiratory control with alpha-glycerophosphate in a patient with ragged-red fibers. Further interpretation of this defect and its significance must await more studies to determine whether this muscle mitochondrial abnormality is a common finding in the disorders in which ragged-red fibers are encountered.

Adenosine Triphosphatases↗