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D Yee

Publications and source records attributed to D Yee.

At least 73 records · Page 4Linked to original sources
PubMed1994

Detection of insulin-like growth factor binding proteins (IGFBPs) by ligand blotting in breast cancer tissues.

Eighty breast cancer specimens were examined for insulin-like growth factor binding protein (IGFBP) expression by ligand blotting. Five distinct IGFBP species were found: a doublet at 48 and 44 kDa was IGFBP-3, the 34-kDa band was IGFBP-2, and a band at 24 kDa was IGFBP-4. A 32-kDa band was compatible with the migration position reported for IGFBP-5. IGFBP-3 was inversely correlated with ER expression, while IGFBP-4 was positively correlated with both ER and PgR. IGFBP-4 was also inversely correlated with S-phase fraction. Thus, IGFBP expression correlates with other parameters of breast cancer biology and may play a role in regulating tumor growth.

Breast Neoplasms↗
PubMed1994

The insulin-like growth factor system as a target in breast cancer.

Evidence from several experimental systems has shown that the insulin-like growth factors (IGFs) can stimulate breast cancer proliferation. Since IGF action is mediated by interaction with specific cell surface receptors, interruption of these signalling pathways could result in inhibition of cellular growth. In all extracellular fluids, the IGFs are associated with high affinity binding proteins, the IGFBPs can bind the IGFs and prevent receptor activation, and thus might have a role in a targeted approach to breast cancer therapy. Here we present our studies using IGFBP-1 to inhibit growth of the breast cancer cell line MCF-7.

Animals↗
PubMed1994

Case report: use of insulin-like growth factor-I gene expression to distinguish between breast and ovarian cancer.

Autocrine expression of polypeptide growth factors may be important in the growth regulation of cancer cells. Different growth factor activities have been identified in a variety of tumors. This article describes a case of malignant ascites in a patient recently treated for breast cancer. The use of growth factor mRNA expression as a factor to differentiate between breast and ovarian origins of cancer cells contained in malignant ascites was examined. Expression of insulin-like growth factor-I (IGF-I), IGF-II, and transforming growth factor alpha mRNA was examined by ribonuclease protection assay. The tumor cells expressed IGF-II and transforming growth factor alpha, but not IGF-I mRNA. This pattern of growth factor expression is compatible with a breast cancer primary of the malignant cells contained in the ascites fluid. Therefore, IGF-I mRNA expression may be useful in distinguishing between adenocarcinomas of breast or ovarian origins.

Adenocarcinoma↗
PubMed1994

Insulin-like growth factor binding protein 1 expression inhibits insulin-like growth factor I action in MCF-7 breast cancer cells.

Interactions between insulin-like growth factor I (IGF-I) and the type of I IGF receptor may be affected by high-affinity extracellular binding proteins. To date, six distinct IGF binding proteins (IGFBPs) have been identified, but their physiological roles are not well understood. For example, depending on experimental conditions, IGFBP-1 has been shown to both enhance and inhibit IGF-I mediated mitogenesis. We have previously shown that excess exogenous IGFBP-1 inhibited IGF-I mediated growth of MCF-7 cells. In this study, we examined whether or not endogenously expressed IGFBP-1 could interfere with IGF-I mediated growth of MCF-7 cells. Cells were stably transfected with an IGFBP-1 expression vector. IGFBP-1 mRNA was produced by the cells, and protein was detected in the conditioned media by ligand blot and immunoblot. Type I IGF receptor could not be phosphorylated by IGF-I in cells expressing IGFBP-1; however, an IGF-I analogue (Arg-3-IGF-I), which cannot complex with IGFBPs, stimulated receptor phosphorylation. IGF-I did not stimulate cell growth in IGFBP-1 expressing cells. These results suggest that IGFBP-1 expression in MCF-7 breast cancer cells inhibits IGF-I induced growth by interrupting the interaction between IGF-I and its receptor.

Breast Neoplasms↗
PubMed1994

Inhibition of estrogen-induced breast cancer cell proliferation by reduction in autocrine transforming growth factor alpha expression.

Breast cancer cell lines have been shown to secrete transforming growth factor alpha (TGF alpha) and other polypeptide growth factors in response to estrogen (E2) stimulation. In this study, we investigated whether cellular-derived TGF alpha mediates the growth-stimulatory effects of E2 in ER-positive breast cancer cells. To test this hypothesis, we introduced an antisense TGF alpha mRNA expression vector under control of a human metallothionein promoter into E2-responsive T47D human breast cancer cells. In stably transfected cells, cadmium induced antisense mRNA and reduced expression of TGF alpha mRNA and protein in antisense clones (AS1). TGF alpha expression was increased in sense clones (S2), while wild-type T47D cells (W3) or pSV2 neomycin resistance-transfected cells showed no change in TGF alpha expression in response to cadmium. The basal proliferative capacity of antisense transfected cells was equivalent to that of the wild-type. E2 increased TGF alpha synthesis and cell proliferation in transfected and wild-type cells. In AS1 cells, the simultaneous addition of cadmium with E2 blocked most of the E2-induced increase in TGF alpha mRNA and protein and nearly abolished the stimulatory effects of E2 on DNA synthesis and cell number. In contrast, no reduction in cell proliferation was observed with cadmium in antisense-transfected cells with a low level of antisense expression or in the S2 or W3 cells. Our results are compatible with the hypothesis that autocrine production of TGF alpha may be an important contributor to E2-induced growth in T47D cells.

Breast Neoplasms↗
PubMed1993

Expression of insulin-like growth factor binding proteins in human breast cancer correlates with estrogen receptor status.

The insulin-like growth factors (IGFs) have been implicated in the growth regulation of human breast cancer. Since the IGFs are associated with specific binding proteins (IGFBPs) which may modulate receptor/ligand interactions, production of IGFBPs by breast cancer cells could alter their IGF-dependent growth. This study examined the expression of IGFBPs 4, 5, and 6 in eight breast cancer cell lines (BCCLs) using ribonuclease (RNase) protection assays. IGFBP-4 mRNA was detected in all BCCLs studied. IGFBP-5 expression was higher in estrogen receptor (ER) positive cells, while IGFBP-6 mRNA was detected in only two ER negative BCCLs. We also found that E2 treatment enhanced the expression of IGFBPs 2, 4, and 5 in T47-D cells. We next studied IGFBP mRNA expression in 40 primary breast tumors. All tumors expressed mRNA for IGFBPs 2-6 but none expressed IGFBP-1 message. IGFBP-3 expression was higher in ER negative tumors, while that of IGFBP-4 and -5 was higher in ER positive specimens. These differences were statistically significant (P < .05). Ligand blot analysis of tumor extracts confirmed the presence of IGFBPs in breast cancer tissues. Thus, differential IGFBP expression in ER positive and negative tumors suggests an important role for this protein in breast cancer biology.

Blotting, Western↗
PubMed1993

Recombinant insulin-like growth factor binding protein-1 inhibits IGF-I, serum, and estrogen-dependent growth of MCF-7 human breast cancer cells.

The insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells and their activity is modulated by high affinity binding proteins (IGFBPs). We have recently shown that IGFBP-1 purified from human amniotic fluid neutralizes IGF-I-dependent growth of MCF-7 cells. In this study we examined the effects of recombinant IGFBP-1 (rBP-1) on IGF-I, estradiol (E2), and serum-induced monolayer and anchorage independent growth (AIG) of MCF-7 cells. Under serum-free conditions, rBP-1 had no effect on MCF-7 basal monolayer growth. However, 40 nM rBP-1 completely blocked the mitogenic action of both IGF-I and 5% charcoal stripped serum (CSS). This concentration of rBP-1 partially inhibited E2-induced growth, while 80 nM rBP-1 completely abolished E2 mitogenicity. The addition of either excess IGF-I or 5 nM [Arg3]IGF-I, a species that does not bind IGFBPs, neutralized rBP-1 inhibitory effects. In AIG assays, 80 nM rBP-1 reduced colony number by at least 70% and decreased colony size in all treatment groups compared to control. We examined rBP-1 effects on both IGF-I binding to MCF-7 membranes and activation of type I IGF receptor (IGFR1) and found that 80 nM rBP-1 reduced IGF-I receptor binding to levels of nonspecific binding and completely abolished ligand-dependent IGFR1 phosphorylation. However, neither treatment with 5% CSS nor exposure to E2 resulted in IGFR1 phosphorylation suggesting that different mechanism(s) are responsible for rBP-1 inhibitory action under this condition. Our data suggest rBP-1 may serve as an antagonist of human breast cancer growth by interfering with growth factor-mediated cell proliferation.

Analysis of Variance↗
PubMed1993

Phase II trial of 13-cis-retinoic acid plus interferon-alpha in recurrent head and neck cancer.

13-cis-retinoic acid (isotretinoin) and interferon-alpha have limited activity as single agents in advanced cancer. Preclinical data indicate that these agents have different mechanisms of action and, in combination have greater activity (that is, the ability to modulate growth and differentiation) in a number of malignant cell types than either agent alone. In clinical trials, the new biological regimen of 13-cis-retinoic acid and interferon-alpha was shown to have major activity in advanced squamous cell carcinoma of the skin and cervix. We conducted a phase II trial of this regimen in recurrent squamous cell carcinoma of the head and neck. Of the 21 evaluable patients, none had a complete response, and only one had a partial response (5%). Two patients had minor responses, four had stable disease, and 14 experienced disease progression. Five patients developed grade 3 toxic effects, including skin toxicity, fatigue, headache, and anorexia/weight loss. The median survival duration was 25.5 weeks (range, 4-95). The combination of 13-cis-retinoic acid and interferon-alpha at this dose and schedule is ineffective for the treatment of recurrent squamous cell carcinoma of the head and neck.

Adult↗
PubMed1993

Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system.

N-CAM is abundantly expressed in the nervous system in the form of numerous structural variants with characteristic distribution patterns and functional properties. N-CAM-180, the variant having the largest cytoplasmic domain, is expressed by all neurons. The N-CAM-180-specific exon 18 has been deleted to generate homozygous mice unable to express this N-CAM form. The most conspicuous mutant phenotype was in the olfactory bulb, where granule cells were both reduced in number and disorganized. In addition, precursors of these cells were found to be accumulated at their origin in the subependymal zone at the lateral ventricle. Analysis of the mutant in this region suggests that the mutant phenotype involves a defect in cell migration, possibly through specific loss of the polysialylated form of N-CAM-180, which is expressed in the migration pathway. Subtle but distinct abnormalities also were observed in other regions of the brain.

Actins↗
PubMed1993

Regulation of insulin-like growth factor binding proteins in ovarian cancer cells by oestrogen.

Insulin-like growth factor-I (IGF-I), its receptor and its binding proteins are expressed by ovarian cancer cells. In this study, we examined oestradiol (E2) regulation of IGF-I and IGF binding proteins (IGFBP) in an oestrogen-responsive ovarian cancer cell line, PE04. In serum-free conditions, PE04 cell monolayer growth was increased 1.64-fold by 3 nmol/l E2 compared with controls, although IGF-I mRNA levels were not increased. In contrast to IGF-I mRNA, IGFBP mRNA was regulated by E2. E2 caused a marked decrease in IGFBP-3 RNA, but IGFBP-2, -4 and -6 levels were only minimally depressed. IGFBP-5 mRNA levels were increased by E2. Tamoxifen had less effect on IGFBP mRNA regulation. Ligand blotting showed that E2 reduced IGFBP levels in conditioned media. IGFBP RNA was also detected in human ovarian tissue samples. Thus, IGFBP expression can be regulated in oestrogen-responsive ovarian cancer by E2.

Blotting, Western↗
PubMed1993

In vitro sensitivity testing of human bladder cancers and cell lines to TP-40, a hybrid protein with selective targeting and cytotoxicity.

TP-40 is a hybrid fusion protein produced by recombinant technology and consists of a molecule of transforming growth factor-alpha (TGF-alpha) fused to the Pseudomonas exotoxin PE-40. A panel of human and murine bladder cancer cell lines was found to be universally sensitive in vitro to TP-40 in a clonogenic assay. All lines expressed receptor for epidermal growth factor (EGF), though none demonstrated gene amplification for the EGF receptor. The sensitivity to TP-40 may be blocked by preexposure to EGF. Six human bladder tumors taken directly from patients were all sensitive in vitro to TP-40; these included well-differentiated tumors. TP-40 may prove to be effective as an intravesical agent in bladder cancer via selective targeting to cells that express EGF receptors, as do the majority of human bladder cancers.

ADP Ribose Transferases↗
PubMed1993

Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II).

Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens for some human breast cancer cell lines, and expression of IGF-II mRNA in the oestrogen receptor-positive (ER+) and oestradiol (E2) stimulated human breast cancer cell line T47D is increased by E2, suggesting a role for IGF-II in the mitogenic response to E2. Very little information is available from the literature on the relation between growth inhibition by endocrine therapy and cellular production of IGF-II. Here we report on the effect of E2 and tamoxifen (TAM) on IGF-II mRNA and protein expression in the ER+T61 human breast cancer xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay. Untreated T61 tumours have a high baseline expression of IGF-II mRNA. TAM treatment of T61 tumours, which results in inhibition of tumour growth without tumour regression, reduced IGF-II mRNA expression approximately 10-fold after 48 h of treatment. E2 treatment of T61 tumours, which results in tumour regression, was accompanied by a more pronounced decrease in IGF-II mRNA expression in the tumour cells; 96 h after initiation of E2 treatment, there was almost no detectable IGF-II mRNA. Analyses of IGF-II protein showed that both treatments significantly reduced the concentration of IGF-II protein in the tumours. This down-regulation was found to be specific for IGF-II, since analyses of the effect of E2 on the expression of IGF-I mRNA, 36B4 mRNA, transforming growth factor alpha(TGF-alpha) mRNA, and epidermal growth factor (EGF) receptor mRNA in T61 tumours did not reveal any down-regulation. To further study the relation between inhibition of tumour growth and down-regulation of IGF-II, we exposed T61 tumours to a monoclonal antibody, alpha-IR3, which abolishes the physiological effect of IGF-I and IGF-II by blocking the binding of both growth factors to the type I IGF receptor. Treatment with alpha-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Development of predictive models of laboratory animal growth using artificial neural networks.

Traditional regression analysis of body weight growth curves encounters problems when the data are extremely variable. While transformations are often employed to meet the criteria of the analysis, some transformations are inadequate for normalizing the data. Regression analysis also requires presuppositions regarding the model to be fit and the techniques to be used in the analysis. An alternative approach using artificial neural networks is presented which may be suitable for developing predictive models of growth. Neural networks are simulators of the processes that occur in the biological brain during the learning process. They are trained on the data, developing the necessary algorithms within their internal architecture, and produce a predictive model based on the learned facts. A dataset of Sprague-Dawley rat (Rattus norvegicus) weights is analyzed by both traditional regression analysis and neural network training. Predictions of body weight are made from both models. While both methods produce models that adequately predict the body weights, the neural network model is superior in that it combines accuracy and precision, being less influenced by longitudinal variability in the data. Thus, the neural network provides another tool for researchers to analyze growth curve data.

Algorithms↗
PubMed1993

Prognostic indicators in early breast cancer.

Approximately 115,000 new cases of axillary node negative breast cancer were diagnosed in this country last year. Since about 20-30% of these patients will ultimately relapse and die of their disease, adjuvant systemic therapy has been advocated for this group to decrease the relapse rate and prolong survival. However, although most clinical trials have demonstrated a modest impact on disease recurrence, the available data have failed to show consistent improvements in overall survival and does not justify the generalized use of systemic treatment in this patient subgroup. For this reason, a plethora of prognostic factors have been described to identify those patients with a higher risk of recurrence to concentrate therapeutic options in this specific group. Of all the disease prognosticators studied, tumor size, nuclear grade, and proliferative indexes appear to correlate well with tumor recurrence. In addition, biologic characteristics of primary tumors such as the presence of hormone and growth factor receptors, secretion of specific polypeptides and proteases, expression of proto-oncogenes, and abnormalities in tumor suppressor genes have been shown to be potentially useful as prognostic indicators in patients with early breast cancer. Despite these provocative data, larger clinical trials are necessary before incorporating these parameters in the routine evaluation of patients with axillary node negative breast cancer.

Breast Neoplasms↗