The insulin-like growth factor I receptor (IGF-IR) is a ubiquitous and multifunctional tyrosine kinase that has been implicated in breast cancer development. In estrogen receptor (ER)-positive breast tumors, the levels of the IGF-IR and its substrate, insulin-receptor substrate 1 (IRS-1), are often elevated, and these characteristics have been linked with increased radioresistance and cancer recurrence. In vitro, activation of the IGF-IR/IRS-1 pathway in ER-positive cells improves growth and counteracts apoptosis induced by anticancer treatments.
View Article and Find Full Text PDFHyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells.
View Article and Find Full Text PDFObjective: To assess endothelial dysfunction in patients with MS and to investigate whether plasma from patients with MS induces endothelial cell dysfunction in vitro.
Background: Endothelial cell dysfunction may contribute to the pathogenesis of MS. Elevations of soluble adhesion molecules intracellular adhesion molecule, vascular cell adhesion molecule, and platelet-endothelial cell adhesion molecule-1 (CD31) have been reported as markers of blood-brain barrier (BBB) damage in MS, but direct assay of endothelium has been difficult.
Control of hyperphosphatemia in renal failure is often difficult to achieve. Although calcium-containing phosphate binders have become the preferred phosphate binders, many patients require the addition of an aluminum-containing phosphate binder (APB). Enhanced aluminum absorption has been noted when APBs are administered with citrate-containing products such as citrate/citric acid solution (CCA).
View Article and Find Full Text PDFThis study was carried out from 1997 to 1998 along a selected coastal area near Catania to ascertain bacteriological and virological quality of marine waters. 44 seawater samples, collected from 4 stations, were assayed for the presence of total and fecal coliforms, fecal streptococci, coliphages, Salmonellae and enteric viruses. Two stations localized at canal outfalls showed high levels of fecal pollution.
View Article and Find Full Text PDFAim Of The Study: to compare AG versus MAC using propofol & remifentanil in a day surgery setting evaluating intra and postoperative clinical conditions and emergence times.
Methods: Propofol and remifentanil, either for general anesthesia (AG) then conscious sedation (MAC), have been administered to 218 patients undergoing mainly plastic or proctologic surgery as day hospital. AG was induced with propofol 1.
Endothelial injury is believed to be a key initiating event in the pathogenesis of thrombotic thrombocytopenic purpura (TTP), leading to platelet activation and formation of platelet-rich thrombi in microvasculature. However, the nature of endothelial injury in TTP is poorly defined and clinical assays to rapidly and reliably monitor endothelial damage are not readily available. Using flow cytometry, we measured endothelial microparticles (EMPs) generated from cultured renal and brain microvascular endothelial cells (MVECs) during activation and apoptosis, and evaluated the effect of TTP plasma on them.
View Article and Find Full Text PDFTyrosine kinases and phosphatases are regulators of the steady-state levels of phosphotyrosine proteins and, in this way, are key players in determining the functional state of the cell. As a unique member of the protein tyrosine phosphatase (PTP) superfamily, osteotesticular PTP (OST-PTP) is a receptor protein whose expression is highly regulated during osteoblast differentiation and in response to modulators of bone remodeling such as parathyroid hormone and vitamin D3. To explore the molecular mechanisms and signaling pathways important in the regulation of this gene, we characterized the structural organization of the mouse OST-PTP cDNA and gene and determined its chromosomal localization.
View Article and Find Full Text PDFThe oncogenic SHC proteins are signaling substrates for most receptor and cytoplasmic tyrosine kinases (TKs) and have been implicated in cellular growth, transformation, and differentiation. In tumor cells overexpressing TKs, the levels of tyrosine phosphorylated SHC are chronically elevated. The significance of amplified SHC signaling in breast tumorigenesis and metastasis remains unknown.
View Article and Find Full Text PDFObjective: To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose.
Research Design And Methods: A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH (in variable proportions) administered at mealtime (group 3, n = 8) for 3 months, NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.
Objective: To review briefly the epidemiology, pathophysiology, and current treatment of primary pulmonary hypertension (PPH) and review the available clinical data on epoprostenol in PPH.
Data Sources: A MEDLINE search (January 1966-August 1998) was used to identify case reports and clinical studies pertaining to epoprostenol in PPH. Bibliographic lists were also used.
The pure antiestrogen ICI 182,780 inhibits insulin-like growth factor (IGF)-dependent proliferation in hormone-responsive breast cancer cells. However, the interactions of ICI 182,780 with IGF-I receptor (IGF-IR) intracellular signaling have not been characterized. Here, we studied the effects of ICI 182,780 on IGF-IR signal transduction in MCF-7 breast cancer cells and in MCF-7-derived clones overexpressing either the IGF-IR or its 2 major substrates, insulin receptor substrate 1 (IRS-1) or src/collagen homology proteins (SHC).
View Article and Find Full Text PDFCross-talk between steroid hormones and polypeptide growth factors regulates the growth of hormone-responsive breast cancer cells. For example, in the MCF-7 human breast cancer cell line, insulin up-regulates estrogen receptor (ER) content and binding capacity. Since the insulin receptor (IR) substrate 1 (IRS-1) is one of the core signaling elements transmitting mitogenic and metabolic effects of insulin, we investigated whether IRS-1 is also required for the insulin-induced function of the ER.
View Article and Find Full Text PDFIn order to investigate what is the best single parameter to predict the leukapheretic yield of circulating CD34+ progenitor cells, we retrospectively analyzed data from 68 patients with hematological malignancies who underwent mobilizing therapy. Three main parameters were monitored: total white blood cell (WBC), CD34+ cells, and monocyte counts in peripheral blood (PB) at the same day and at the preceding day of the apheretic procedure. Linear regression analysis revealed a strong correlation between CD34+ cell value in PB just before harvest and the number of CD34+ cells collected (P < 0.
View Article and Find Full Text PDFAnn Pharmacother
December 1997
Objective: To provide an introduction to coronary artery stents and their pharmacologic management, including anticoagulant therapy and newer antiplatelet regimens.
Data Sources: A MEDLINE and current journal search of relevant articles that evaluated coronary stent success rates and anticoagulation or antiplatelet regimens.
Study Selection: Data from the use of primarily the Palmaz-Schatz stent were included.
Hybridization assay and direct immunoassay for detecting Salmonella in contaminated surface waters have been compared with the conventional culture procedure. The 67 samples examined were taken from different rivers in the provinces of Catania and Ragusa. By culture method, Salmonella was isolated in 23 samples (34%), while direct immunoassay revealed the presence of Salmonella in 58 samples (87%) and the hybridization method identified Salmonella in 20 samples (30%).
View Article and Find Full Text PDFObjective: To compare the coronary and cerebral perfusion achieved using a novel method of minimally-invasive, direct cardiac massage to that obtained using bimanual, open-chest cardiac massage.
Design: Prospective, controlled animal study with repeated measures.
Setting: University research laboratory.
The effect of Tri-iodothyronine (T3) administration leading to the precocius differentiation of Sertoli cell in prepuberal rats has been previously shown. The functional maturation of Sertoli cells is associated with changes in androgen metabolism. We have recently demonstrated that T3 influences androgen metabolism in Sertoli cells by inhibiting aromatase activity and reduces drastically the ER contents in peripubertal hypothyroid rats.
View Article and Find Full Text PDFWe report a case of de novo plasma cell leukemia, resistant to standard VMD (vincristine, mitoxantrone, dexamethasone) and CVP (cyclophosphamide, vincristine and prednisone) protocols, treated with a chemotherapy intensification regimen (high-dose cyclophosphamide, modified EDAP, Dexa-BEAM) and peripheral blood stem cell transplantation, performed using fractionated total body irradiation and high dose melphalan. The patient is currently alive and well, in very good partial remission 12 months after transplant and 22 months after diagnosis, disclosing a significant proportion of bone marrow and peripheral blood CD3+, CD8+, CD57+, HLA-Dr+ large granular lymphocytes with cytotoxic activity against neoplastic plasma cells.
View Article and Find Full Text PDFBackground: Hematopoietic progenitor cells (HPC), identified by expression of the CD34 surface antigen, show morphological and phenotypic heterogeneity in bone marrow (BM) and peripheral blood (PB).
Methods: CD34+ HPC subpopulations present in 18 PB leukaphereses after high-dose chemotherapy in cancer patients and in 11 BM samples from patients with stage IA lymphoma were characterized. In order to identify CD34+ HPC subsets within these two compartments, the expression of lineage- or activation-associated antigens and the c-kit gene product (CD117) was studied by flow cytometry, using a large panel of monoclonal antibodies (MoAb) in double labelling.
The effects of thyroid hormone on androgen metabolism in peripuberal Sertoli cells through the inhibition of estradiol production have been reported previously. It was our intention to investigate further the possible role of thyroid hormone on the interaction between testicular steroids and Sertoli cells by analyzing the effects of triiodothyronine (T3) on estrogen receptor content in 2-, 3- and 4- week-old euthyroid rats. Triiodothyronine treatment (3 micrograms/100 body wt per day) given during the last week prior to sacrifice resulted in reduced testicular growth in 2-week-old animals.
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