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4.
Mediators Inflamm ; 2020: 2707635, 2020.
Article in English | MEDLINE | ID: mdl-32655311

ABSTRACT

Receptor internalization and degradation (RID), is a transmembrane protein coded within the E3 region expression cassette of adenoviruses. RID downregulates the cell surface expression of epidermal growth factor receptor (EGFR), tumor necrosis factor receptor (TNFR), and apoptosis antigen 1 (FAS), causing a reduction of the effects of their respective ligands. In addition, RID inhibits apoptosis by decreasing the secretion of TNF-related apoptosis-inducing ligand (TRAIL) by normal tissue cells. In this article, we report that RID inhibited chemokine expression in human breast cancer cell line MDA-MB-231 but showed no effect in cell line MCF7. These dissimilar results may be due to the different molecular and functional properties of both cell lines. Therefore, it is necessary to replicate this study in other breast cancer cell models.


Subject(s)
Adenovirus E3 Proteins/physiology , Breast Neoplasms/metabolism , Membrane Proteins/physiology , NF-kappa B/metabolism , Transcription Factor AP-1/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Adenoviridae/genetics , Adenovirus E3 Proteins/genetics , Cell Line, Tumor , ErbB Receptors/metabolism , Humans , MCF-7 Cells , Membrane Proteins/genetics , Receptors, Tumor Necrosis Factor/metabolism , Signal Transduction/drug effects , fas Receptor/metabolism
7.
Curr Top Microbiol Immunol ; 273: 113-35, 2004.
Article in English | MEDLINE | ID: mdl-14674600

ABSTRACT

Adenoviruses contain genes that have evolved to control the host immune and inflammatory responses; however, it is not clear whether these genes function primarily to facilitate survival of the virus during acute infection or during its persistent phase. These issues have assumed greater importance as the use of adenoviruses as vectors for gene therapy has been expanded. This review will focus on the mechanism of immune evasion mediated by the proteins encoded within the early region 3 (E3) transcription region, which affect the functions of a number of cell surface receptors including Fas, intracellular cell signaling events involving NF-kappaB, and the secretion of pro-inflammatory molecules such as chemokines. The successful use of E3 genes in facilitating allogeneic transplantation and in preventing autoimmune diabetes in several transgenic mouse models will also be described.


Subject(s)
Adenoviridae Infections/immunology , Adenoviridae/physiology , Adenovirus E3 Proteins/immunology , Adenoviridae/immunology , Adenoviridae Infections/virology , Adenovirus E3 Proteins/genetics , Adenovirus E3 Proteins/physiology , Animals , Autoimmune Diseases/immunology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Gene Expression Regulation , Humans
8.
Rev Neurol ; 37(5): 438-40, 2003.
Article in Spanish | MEDLINE | ID: mdl-14533092

ABSTRACT

INTRODUCTION: Gangliogliomas are infrequent neuronoglial tumours which present in youngsters and are usually located in the temporal lobe. They usually appear with epileptic seizures and prognosis after surgical excision is usually good. The anaplastic forms are even less frequent and prognosis is poorer. The onset of epileptic seizures during the early post-natal period means that the clinician has to resort to a broad differential diagnosis. CASE REPORT: Hours after a preterm birth, at the 32nd week of gestation, a 35-year-old primipara began to suffer seizures and also presented arterial hypertension, proteinuria and a low platelet count. A cranial computerized tomography scan was carried out where a left frontal hypodense lesion was observed. Transcranial echo Doppler scan showed medium speeds and suggested eclampsia. The seizures, however, recurred during the days that followed and a magnetic resonance scan of the head revealed a lesion with nodular contrast enhancement, which was excised, and finally an anatomopathological diagnosis of an anaplastic ganglioglioma was reached. DISCUSSION: The toxemia of pregnancy, which gave rise to a vasogenic cerebral edema, accelerated the clinical onset of a brain tumour during the post-natal period. A ganglioglioma, although infrequent, is always a possibility to be borne in mind in young patients.


Subject(s)
Anaplasia/pathology , Brain Neoplasms , Frontal Lobe/pathology , Ganglioglioma , Pre-Eclampsia/complications , Adult , Brain Neoplasms/etiology , Brain Neoplasms/pathology , Diagnosis, Differential , Female , Ganglioglioma/etiology , Ganglioglioma/pathology , Humans , Magnetic Resonance Imaging , Pregnancy , Prognosis , Seizures/etiology
9.
Rev. neurol. (Ed. impr.) ; 37(5): 438-440, 1 sept., 2003. ilus
Article in Spanish | IBECS | ID: ibc-155698

ABSTRACT

Introducción. El ganglioglioma es un tumor neuronoglial poco frecuente, de presentación en jóvenes y localización preferente en el lóbulo temporal. Suelen manifestarse con crisis epilépticas y el pronóstico tras la resección quirúrgica suele ser bueno. Las formas anaplásicas son aun menos frecuentes y de peor pronóstico. El inicio de crisis epilépticas durante el puerperio precoz obliga a plantear un diagnóstico diferencial amplio. Caso clínico. Horas después de un parto pretérmino, tras 32 semanas de gestación, una primípara de 35 años debutó con una convulsión, y presentó además hipertensión arterial, proteinuria y plaquetopenia. Se realizó una tomografía computarizada craneal donde se objetivó una lesión hipodensa frontal izquierda. Una ecografía Doppler transcraneal mostró velocidades medias, y sugirió una eclampsia. Sin embargo, en los días posteriores recurrieron las crisis, por lo que se realizó una resonancia magnética de cráneo que mostró una lesión con captación nodular de contraste, que se resecó, y se llegó al diagnóstico anatomopatológico de ganglioglioma anaplásico. Discusión. Una toxemia gravídica, que desencadenó un edema cerebral vasogénico, pudo precipitar el inicio clínico de un tumor cerebral durante el puerperio. Un ganglioglioma, aunque raro, es siempre una posibilidad a considerar en pacientes jóvenes (AU)


Introduction. Gangliogliomas are infrequent neuronoglial tumours which present in youngsters and are usually located in the temporal lobe. They usually appear with epileptic seizures and prognosis after surgical excision is usually good. The anaplastic forms are even less frequent and prognosis is poorer. The onset of epileptic seizures during the early post-natal period means that the clinician has to resort to a broad differential diagnosis. Case report. Hours after a preterm birth, at the 32nd week of gestation, a 35-year-old primipara began to suffer seizures and also presented arterial hypertension, proteinuria and a low platelet count. A cranial computerized tomography scan was carried out where a left frontal hypodense lesion was observed. Transcranial echoDoppler scan showed medium speeds and suggested eclampsia. The seizures, however, recurred during the days that followed and a magnetic resonance scan of the head revealed a lesion with nodular contrast enhancement, which was excised, and finally an anatomopathological diagnosis of an anaplastic ganglioglioma was reached. Discussion. The toxemia of pregnancy, which gave rise to a vasogenic cerebral edema, accelerated the clinical onset of a brain tumour during the post-natal period. A ganglioglioma, although infrequent, is always a possibility to be borne in mind in young patients (AU)


Subject(s)
Humans , Female , Adult , Anaplasia/pathology , Brain Neoplasms/etiology , Brain Neoplasms/pathology , Frontal Lobe/pathology , Ganglioglioma/etiology , Ganglioglioma/pathology , Pre-Eclampsia , Diagnosis, Differential , Magnetic Resonance Imaging , Pregnancy , Prognosis , Seizures/etiology
17.
J Cell Biochem ; 71(2): 189-203, 1998 Nov 01.
Article in English | MEDLINE | ID: mdl-9779818

ABSTRACT

We analyzed the expression of hexose transporters in human testis and in human, rat, and bull spermatozoa and studied the uptake of hexoses and vitamin C in bull spermatozoa. Immunocytochemical and reverse transcription-polymerase chain reaction analyses demonstrated that adult human testis expressed the hexose transporters GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Immunoblotting experiments demonstrated the presence of proteins of about 50-70 kD reactive with anti-GLUT1, GLUT2, GLUT3, and GLUT5 in membranes prepared from human spermatozoa, but no proteins reactive with GLUT4 antibodies were detected. Immunolocalization experiments confirmed the presence of GLUT1, GLUT2, GLUT3, GLUT5, and low levels of GLUT4 in human, rat, and bull spermatozoa. Each transporter isoform showed a typical subcellular localization in the head and the sperm tail. In the tail, GLUT3 and GLUT5 were present at the level of the middle piece in the three species examined, GLUT1 was present in the principal piece, and the localization of GLUT2 differed according of the species examined. Bull spermatozoa transported deoxyglucose, fructose, and the oxidized form of vitamin C, dehydroascorbic acid. Transport of deoxyglucose and dehydroascorbic acid was inhibited by cytochalasin B, indicating the direct participation of facilitative hexose transporters in the transport of both substrates by bull spermatozoa. Transport of fructose was not affected by cytochalasin B, which is consistent for an important role for GLUT5 in the transport of fructose in these cells. The data show that human, rat, and bull spermatozoa express several hexose transporter isoforms that allow for the efficient uptake of glucose, fructose, and dehydroascorbic acid by these cells.


Subject(s)
Ascorbic Acid/metabolism , Hexoses/metabolism , Monosaccharide Transport Proteins/metabolism , Spermatozoa/metabolism , Animals , Base Sequence , Cattle , DNA Primers , Humans , Male
18.
Blood ; 91(3): 1037-43, 1998 Feb 01.
Article in English | MEDLINE | ID: mdl-9446667

ABSTRACT

We studied the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in the human prostate carcinoma cell line LNCaP and looked for its presence in normal and neoplastic human prostatic tissue. The GM-CSF receptor is composed of two subunits, alpha and beta. While the isolated alpha subunit binds GM-CSF at low-affinity, the isolated beta subunit does not bind GM-CSF by itself; but complexes with the alpha subunit to form a high-affinity receptor. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed expression of mRNAs encoding the alpha and beta subunits of the GM-CSF receptor in LNCaP cells, and the presence of the alpha and beta proteins was confirmed by immunolocalization with anti-alpha and anti-beta antibodies. Receptor binding studies using radiolabeled GM-CSF showed that LNCaP cells have about 150 high-affinity sites with a kd of 40 pmol/L and approximately 750 low-affinity sites with a kd of 2 nmol/L. GM-CSF signaled, in a time- and dose-dependent manner, for protein tyrosine phosphorylation and induced the proliferation of the LNCaP cells. Immunolocalization studies showed low level expression of GM-CSF alpha and beta subunits in normal prostate tissue, with substantial expression in benign prostatic hyperplasia and prominent expression in neoplastic prostate tissue. Maximal expression of both subunits was observed in prostatic carcinomas metastatic to lymph node and bone. Tumor cells that stained positively with anti-alpha subunit antibodies were also reactive with anti-beta subunit antibodies, indicating that they express high-affinity GM-CSF receptors. Our data show that the LNCaP cells express functional GM-CSF receptors and that prostatic carcinomas have prominent GM-CSF receptor expression. These findings imply that both hyperplastic and neoplastic prostatic tissues may be responsive to GM-CSF.


Subject(s)
Gene Expression , Prostatic Neoplasms/chemistry , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Epithelium/chemistry , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , HL-60 Cells/metabolism , Humans , Immunoenzyme Techniques , Male , Phosphorylation , Phosphotyrosine/metabolism , Polymerase Chain Reaction , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/metabolism , RNA, Messenger/analysis , RNA-Directed DNA Polymerase , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/analysis , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Signal Transduction , Tumor Cells, Cultured
19.
Proc Natl Acad Sci U S A ; 93(5): 1847-52, 1996 Mar 05.
Article in English | MEDLINE | ID: mdl-8700847

ABSTRACT

The primary metabolic characteristic of malignant cells is an increased uptake of glucose and its anaerobic metabolism. We studied the expression and function of the glucose transporters in human breast cancer cell lines and analyzed their expression in normal and neoplastic primary human breast tissue. Hexose uptake assays and immunoblotting experiments revealed that the breast carcinoma cell lines MCF-7 and MDA-468 express the glucose transporters GLUT1 and GLUT2, isoforms expressed in both normal and neoplastic breast tissue. We also found that the breast cancer cell lines transport fructose and express the fructose transporter GLUT5. Immunolocalization studies revealed that GLUT5 is highly expressed in vivo in human breast cancer but is absent in normal human breast tissue. These findings indicate that human breast cancer cells have a specialized capacity to transport fructose, a metabolic substrate believed to be used by few human tissues. Identification of a high-affinity fructose transporter on human breast cancer cells opens opportunities to develop novel strategies for early diagnosis and treatment of breast cancer.


Subject(s)
Breast Neoplasms/metabolism , Monosaccharide Transport Proteins/metabolism , Breast/metabolism , Deoxyglucose/metabolism , Epithelium/metabolism , Fructose/metabolism , Glucose Transporter Type 1 , Glucose Transporter Type 2 , Glucose Transporter Type 5 , Humans , Immunologic Techniques , Monosaccharide Transport Proteins/immunology , Tumor Cells, Cultured
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