Antitumor activity of the novel human breast cancer growth inhibitor, mammary-derived growth inhibitor-related gene, MRG

A novel human tumor growth inhibitor was identified by differential cDNA sequencing. The predicted amino acid sequence of this tumor-suppressing factor has a significant sequence homology to mouse mammary-derived growth inhibitor and thus was named mammary-derived growth inhibitor-related gene (MRG). MRG was found to be expressed in normal and benign human breast tissues but not in breast carcinomas. In situ hybridization analysis demonstrated a stage-specific MRG expression as follows. MRG was barely detectable in breast carcinomas, showed partial and weak expression in benign hyperplasia, but was expressed at a high level in normal breast epithelial cells. To determine if MRG can modulate in vivo growth of human breast cancers, we transfected a full-length MRG cDNA into MDA-MB-231 human breast cancer cells and studied the orthotopic growth of MRG transfectants versus control transfectants in the mammary fat pad of athymic nude mice. Overexpression of MRG in human breast cancer cells significantly suppressed cell proliferation in vitro and tumor growth in an orthotopic nude mouse model. These results suggest that MRG has tumor-suppressing activity, and the loss of MRG expression may be involved in the development and progression of breast cancer.     

Repressive adaptation in children with cancer.

The constructs of repressive adaptive style and avoidant coping (blunting) were assessed as possible explanatory factors for previously reported findings of lower self-reported depression in children with cancer. Pediatric oncology patients 7–16 years old (n?=?107) and healthy control participants (n?=?442) completed measures of depressive symptoms, trait anxiety, defensiveness, and approach and avoidant coping. Oncology patients scored significantly lower on measures of depression and trait anxiety, and higher on defensiveness. Applying the adaptive style paradigm, the oncology group showed a significant excess of repressors. Depressive symptoms differed as a function of adaptive style, with repressors demonstrating the lowest levels of self-reported depression. Children with cancer also reported greater use of blunting, but this difference was small and appeared unrelated to depression scores. Within the cancer group, repressive adaptation was unrelated to time elapsed since diagnosis. These findings are discussed with reference to the ongoing controversy regarding cancer–personality style associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Detection of restricted junctional diversity of peripheral T cells in SLE patients by spectratyping

Three patients presented with unilateral sensori-neural hearing disturbance as the initial symptom of cerebellar tumors: a 19-year-old female with a medulloblastoma (Case 1), a 45-year-old male with a cerebellar low-grade glioma (Case 2), and a 49-year-old female with a cerebellaer hemangioblastoma (Case 3). In Cases 1 and 2, the whole length of the eight cranial nerve was intact according to magnetic resonance imaging and intraoperative findings. In Case 3, the intracerebellar tumor had bulged into the cerebellopontine cistern, compressing the eighth cranial nerve near the brainstem. Auditory evoked brainstem responses showed only the first wave in all three patients, and the following waves could not be discriminated. Unilateral sensori-neural hearing disturbance occurs very rarely in patients with intramedullary cerebellar lesions because the auditory neural pathway is bilaterally innervated. Intramedullary tumors may cause unilateral sensori-neural hearing disturbance by infiltrating or causing edematous changes of the eighth cranial nerve or the cochlear nucleus in the brainstem, or by compressing the nerve in the cistern. The symptoms are the same as those of acoustic neurinoma, so intramedullary cerebellar tumors should be considered in the differential diagnosis of unilateral sensorineural hearing disturbance.     

Epidermal growth factor and laminin receptors contribute to migratory and invasive properties of gliomas

Gliomas are characterized by their extensive invasion into the brain parenchyma. Recently it has been shown that normal brain cells can produce laminin, fibronectin and collagen type IV when confronted by invading glioma cells. Laminin stimulates cell migration of several human glioma cell lines in vitro. This migration can be inhibited by adding blocking monoclonal antibodies (MAbs) against the most expressed integrin subunits, alpha3 and beta1. Previous studies have shown that glioma cell migration, invasion and growth are stimulated by epidermal growth factor (EGF). However, MAb directed against the EGF receptor (EGFR) did only partly inhibit the invasive process in vitro. Since laminin has regional peptide homology with EGF (EGF-like repeats), the present work was aimed at studying how two human glioma cell lines exposed to antibodies to the EGFR, reacted to laminin stimulated migration. Furthermore, we wanted to study which role the EGFR and the laminin receptor integrin subunits alpha3 and beta1 play during glioma cell invasion. EGFR expression of two glioma cell lines, AN1/lacZ and U-251/lacZ was studied by flow cytometry and immunofluorescence microscopy. A cell migration assay was used to study effects of MAbs against EGFR on migration from laminin-stimulated tumor spheroids. Tumor cell invasion was evaluated by using an in vitro co-culture model, where normal fetal brain cell aggregates were confronted with multicellular tumor spheroids. The results show that both cell lines expressed EGFR, AN1/lacZ 4-fold more than U-251/lacZ. MAb against EGFR inhibited the laminin-stimulated migration only from AN1/lacZ spheroids. MAbs against alpha3 and beta1 integrin subunits inhibited glioma cell invasion in vitro. The present work indicates possible connections between laminin-stimulated cell migration and the EGFR expression on glioma cells. These elements contribute to the characteristic features of glioma cells and may be an important part of the complex relationships between growth factors, integrins and extracellular matrix during glioma cell invasion.     

Economic organization of medicine and the Committee on the Costs of Medical Care

PURPOSE: To directly visualize and evaluate the aqueous block copolymeric micelles, poly(ethylene oxide)-poly(beta-benzyl L-aspartate) (PEO-PBLA) chemically conjugated with pyrene fluorescence molecule, by nanotechnology of atomic force microscopy (AFM). METHODS: The block copolymers' PEO-PBLA-Pyrene was first synthesized by reacting with pyrene sulfonyl chloride and PEO-PBLA in tetrahydrofuran (THF) solution and were identified by GPC reflect index, UV and fluorescence detectors. The characterization of physical and chemical properties of PEO-PBLA-Pyrene polymeric micellar solution were examined by the dynamic light scattering (DLS) and critical micelles concentrations (CMC). In addition, the nanotechnology of AFM was used to directly visualize the size and shape of nanopolymeric micelles. RESULTS: The pyrene fluorescence molecule were successfully conjugated at the amino group of the end of PBLA chain by GPC with three different detectors. The size of the aqueous PEO-PBLA-Pyrene polymeric micelles was detected around 57 nm with unimodal distribution by DLS measurement. As a result of this finding, the CMC test was also found out that the fluorescence intensity was increasing around 0.01 approximately 0.05 mg/ml. Using AFM evaluation of polymeric micellar solution, the morphology of aqueous PEO-PBLA-Pyrene polymeric micelles was observed on round shape and with the narrow dispersity of size range 50 approximately 80 nm. CONCLUSIONS: The presence of PEO-PBLA copolymers with pyrene in an aqueous system formed in a spherical and nano range of polymeric micelles.     

Malignant cutaneous melanoma associated with neurofibromatosis in two sisters from a family with familial atypical multiple mole melanoma syndrome. Case reports and review of the literature

Two cases of malignant melanoma associated with neurofibromatosis in two first-degree female relatives from a family with familial atypical multiple mole melanoma (FAMMM) syndrome are presented. The types of neurofibromatosis and the FAMMM syndrome are discussed in relation to these cases and the family genealogic tree. Although the FAMMM syndrome could probably be seen as the underlying disease in the current cases, review of literature has failed to establish a clear relation. Research into pigmentary disturbance in neurofibromatosis is necessary to give a final explanation. To our knowledge, this is the first report in literature describing the familial occurrence of both diseases and it might present an addition to the tumor spectrum in the FAMMM syndrome.     

Chloroquine-induced venodilation in human hand veins

OBJECTIVE: Hypotension induced by parenteral administration of chloroquine is a common and serious adverse effect of this drug. Our aim was to investigate whether chloroquine produces venodilation in vivo and to explore the underlying mechanisms. METHODS: Vascular effects of chloroquine were studied in healthy volunteers with use of the dorsal hand vein technique at the Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System. We studied 22 healthy volunteers (19 men and three women). Venous responsiveness was determined with the dorsal hand vein technique, which measures the diameter of the vein. RESULTS: Chloroquine was found to produce a dose-dependent relaxation of hand veins preconstricted with the alpha 1-receptor selective agonist phenylephrine. The venodilatory response to chloroquine ranged from 15% +/- 19% at an infusion rate of 0.75 microgram/min to 61% +/- 24% at 48 microgram/min. Venodilation was attenuated by the nitric-oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) so that the dose of chloroquine required to produce 20% venodilation was increased from 3.7 micrograms/min to 15 micrograms/min (p < 0.01). In the presence of a combination of histamine receptor antagonists, there was also a diminution of the vasodilatory response to chloroquine from 72% +/- 5% to 44% +/- 5% at the infusion rate of 96 micrograms/min. The response was further reduced to 33% +/- 7% by the coinfusion of H1-/H2-receptor antagonists with L-NMMA. CONCLUSION: Chloroquine produces venodilation at infusion rates that achieve local concentrations likely similar to those observed systemically after clinically relevant intravenous doses. The date also suggest a role for nitric oxide and histamine release in mediating this response.     

CD45 tyrosine phosphatase activity and membrane anchoring are required for T-cell antigen receptor signaling

T cells that lack the CD45 transmembrane tyrosine phosphatase have a variety of T-cell receptor (TCR) signaling defects that are corrected by reexpression of wild-type CD45 or its intracytoplasmic domains. In this study, a chimeric molecule containing the myristylation sequence of Src and the intracellular portion of CD45, previously shown to restore function in CD45- T cells, was mutagenized to determine if membrane-associated CD45 tyrosine phosphatase activity is required to restore TCR-mediated signaling in CD45- T cells. Abolition of enzymatic activity by substitution of a serine for a critical cysteine in the first catalytic domain resulted in failure of this molecule to restore TCR signaling. Another mutation, in which a single amino acid substitution destroyed the myristylation site, resulted in failure of the chimeric molecule to partition to the plasma membrane. Although expressed at high levels and enzymatically active, this form of intracellular CD45 also failed to restore normal signaling in CD45- T cells. These findings strongly suggest that CD45's function in TCR signaling requires its proximity to membrane-associated tyrosine phosphatase substrates.