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Biomedical subjects

I Arany

Publications and source records attributed to I Arany.

At least 55 records · Page 3Linked to original sources
PubMed1994

Interferon treatment enhances the expression of underphosphorylated (biologically-active) retinoblastoma protein in human papilloma virus-infected cells through the inhibitory TGF beta 1/IFN beta cytokine pathway.

Interferons (IFN) regulate transcription of certain genes playing a role in cell proliferation. Targets of IFN action may include tumor suppressor genes such as the retinoblastoma (RB) gene and cytokines such as transforming growth factor beta 1 (TGF beta 1) and IFN beta which are inhibitors of epithelial cell proliferation. Using reverse transcription followed by PCR amplification, an increase of those growth inhibitory gene mRNA levels (TGF beta 1, IFN beta and RB) were found after interferon treatment in condylomas harboring non-oncogenic human papilloma virus (HPV 6/11) types, in an oncogenic HPV 16-containing cell line, and in a HPV negative, epidermoid carcinoma cell line. In addition, immunodetection by Western blot demonstrated a higher proportion of underphosphorylated (active form) retinoblastoma gene protein (pRB) after IFN treatment due to the decrease in the phosphorylating cdc2 kinase levels. Changes in the phosphorylation pattern of pRB together with the increased expression of those inhibitory genes represent a growth inhibited state in those cells as demonstrated by diminished c-myc expression. Since the extent of c-myc inhibition was significantly lower in the case of oncogenic HPV infection, a role of viral oncoproteins in abrogation of the antiproliferative effect of IFN therapy could be considered. These results demonstrate a new mechanism via which IFNs exert their antiproliferative effect on HPV-infected cells by affecting the expression and phosphorylation of the RB tumor suppressor gene, through the inhibitory TGF beta 1/IFN beta cytokine pathway.

Blotting, Western↗
PubMed1994

Analysis of multiple molecular changes in human endocrine tumours.

To define the molecular changes occurring in endocrine tumours, we have analysed three human endocrine tumours established in our laboratory: BON, a functioning carcinoid tumour from the pancreas; SIM, a nonfunctioning carcinoid of the ileum; and STAN, a pheochromocytoma. A homozygous point mutation of the N-ras gene was identified at codon 61 in BON cells in conjunction with overexpression of N-ras mRNA and protein. BON cells also exhibited increased expression of c-myc and cdc2 kinase mRNA and protein; TGF-beta 1, p53 and retinoblastoma (RB) mRNA and protein levels were decreased. In addition, increased expression of the mdm2 oncogene and both the truncated and the wild-type RB protein were noted in BON. SIM cells exhibited moderately increased N-ras and c-myc mRNA levels along with decreased levels of RB mRNA and protein. Similar to BON and SIM, analysis of STAN showed increased N-ras and c-myc levels. Our data show multiple molecular changes in the three human endocrine tumours with the BON cell line exhibiting the most dramatic changes. Furthermore, our data suggest the existence of different molecular pathways in the pathogenesis of endocrine tumours. These cell lines will provide unique in vitro models to further analyse the significance of these molecular alterations.

Aged↗
PubMed1994

Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene.

OBJECTIVE: This study determined whether genomic amplification of HER-2/neu or mutations of the p53 and ras genes were present in gastrinomas. SUMMARY BACKGROUND DATA: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto-oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. METHODS: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. RESULTS: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. CONCLUSIONS: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

Base Sequence↗
PubMed1994

Alteration in the coding potential and expression of H-ras in human cytomegalovirus-transformed cells.

CMV-transformed cell lines demonstrated a greater level of H-ras RNA (7.5- to 9.5-fold) relative to the level for H-ras in parental cells. Nuclear run off assays showed that the RNA levels for the H-ras gene were regulated at the level of transcriptional initiation. The increased RNA levels for H-ras correlated with the level of p21rasVal-12 in transformed cells, while p21rasVal-12 was below the level of detection in nontransformed cells using Western blot analysis. In addition, an activating mutation was identified in both alleles of the first exon, codon 12 of H-ras resulting in a G:C to T:A transversion in all transformed cell lines examined in this study. These results suggest that the mutated H-ras may be one of the components by which an oncogenic phenotype is maintained in these CMV-transformed cells.

Base Sequence↗
PubMed1993

Direct sequencing of consensus primer generated PCR fragments of human papillomaviruses.

Consensus primers specific for the L1 and E1 regions were used to amplify HPV DNA fragments. These fragments were then directly sequenced using the consensus primers as the sequencing primers. The linking of PCR amplification, direct sequencing, and computer data bank analysis provides a new approach in the detection of different HPVs and has several advantages over existing methodology. These advantages include increased precision in the rapid characterization of known HPVs, detection of mutations, and identification of new HPV types.

Base Sequence↗
PubMed1993

Benign Leydig cell tumor of the testis associated with human papillomavirus type 33 presenting with the sign of Leser-Trélat.

We present a case of a benign testicular Leydig cell tumor and eruptive seborrheic keratosis associated with human papillomavirus type 33 infection. To our knowledge this is the first occurrence of a Leydig cell tumor in a patient with tuberous sclerosis and the second documented case of eruptive seborrheic keratoses (sign of Leser-Trélat) associated with a benign neoplasm.

Adult↗
PubMed1993

Alterations in cytokine/antioncogene expression in skin lesions caused by "low-risk" types of human papillomaviruses.

Even though the "low-risk" human papillomavirus (HPV) diseases, such as condyloma acuminatum, rarely progress to malignancy, their high incidence evidences the need for a better understanding of molecular interactions between these viruses and the epithelium. Our study examined the contribution of altered expression of certain cytokines and antioncogenes to the hyperproliferative properties of HPV-related skin lesions. The "low-risk" human papillomavirus types (HPV 6 or 11) were determined by in situ hybridization and PCR amplification followed by direct sequencing using consensus primers from the highly conserved L1 region in six different condylomas. mRNA levels of certain cytokines (e.g., TGF-beta 1, IFN-beta), tumor suppressor genes (RB, p53), c-myc, epidermal growth factor receptor, and cdc2 kinase were measured by RT/PCR. A characteristic change in mRNA levels of those genes was found in condylomas compared to that of the expression levels of uninfected skin. Western blot experiments demonstrated a higher proportion of the hyperphosphorylated form of RB protein and a higher level of cdc2 kinase and c-myc, but low p53 and TGF-beta 1 levels in condylomas. These data reflect a higher proliferative state of those condylomas compared to the normal skin, suggesting a direct or indirect involvement of "low-risk" HPVs in interaction with the cellular cytokine/antioncogene system providing growth advantage to those infected cells.

Blotting, Western↗
PubMed1992

Antisense proenkephalin cDNA transfection decreases opioid binding in NG 108-15 cells.

The proenkephalin A (PENK) gene codes for several opioid peptides, including Met-enkephalin, an endogenous ligand of opioid receptors. These peptides are thought to play an important role in a variety of neural processes. To study the role of the PENK gene in opioid related processes, an antisense sequence of PENK gene was subcloned into pSVL SV 40 late promoter expression vector and stably transfected into NG 108-15 cells, which contain opioid receptors. The sense orientation of the same fragment was also cloned and transfected, serving as a control. The presence and expression of transfected recombinant plasmids in NG 108 cells were confirmed by DNA and RNA PCR and by subsequent sequencing. Surprisingly, the endogeneous PENK message level was found to be 3 times higher in antisense cells than in sense or NG 108 cells. This high steady-state mRNA level seemed to be due to the increased stability of PENK mRNA rather than to an elevated transcription rate. Nevertheless, the level of total Met-enkephalin was found to be reduced in antisense-transfected cells, though free Met-enkephalin content did not differ from sense-transfected or non-transfected cells. We suggest that both the increased PENK message and the unchanged levels of free Met-enkephalin may be the result of compensatory mechanisms induced by translational inhibition by antisense, although the underlying processes remain to be determined. Binding of the opioid ligand [3H]diprenorphine was significantly reduced by 50-80% in the antisense-transfected cell lines, but not in the sense cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1989

N-ras mutation in chemically induced rat brain tumour.

Rat brain tumour was induced by treatment with N-ethyl-nitrosourea. Using Southern blot analysis, restriction fragment length polymorphism of N-ras gene was identified. Comparative studies showed that new restriction site did not occur in the DNA of DMN induced renal and liver tumours. The data suggest that the mutation occurring may be specific to the "target" cell or to the structure of carcinogens.

Animals↗
PubMed1988

Subcellular distribution of hexokinase in leukemic and stimulated lymphoid cells of mice.

The oxygen consumption, subcellular distribution of hexokinase were studied in normal and leukemic spleen cells of AKR mice. High mitochondrial-bound hexokinase activity and O2-consumption were detected in fetal state, in leukemic or BPV-induced lymphoproliferative conditions and after spermine incubation of normal spleen cells. After ConA-treatment, however, all of the hexokinase was found in cytoplasmic fraction and O2-uptake was strongly decreased. Studies on respiration of mitochondria isolated from normal and leukemic cells supported the role of mitochondrial-bound hexokinase in elevated O2-consumption of leukemic cells.

Aging↗
PubMed1987

Further studies on migration and colonization of leukemic lymphoblasts in AKR and HSS inbred mice.

AKR and HSS lymphoid leukemias were transplanted into identical mouse strains and changes in pyruvate kinase activity were measured in thymus, mesenteric lymph node and spleen during the posttransplantation period. The heterogeneity of the cellular density and the size distribution were determined in the HSS spleen cells in order to get more information about the settlement and proliferation of the transplanted leukemic lymphoblasts. The data obtained suggest that this model system may be useful for a follow up the fate of leukemic blast cells in the host animal.

Animals↗
PubMed1985

The radiotherapy of cystic craniopharyngioma with intracystic installation of 90Y silicate colloid.

The authors describe the intracavital treatment with 90Y silicate colloid in 9 cases of cystic craniopharyngioma. The method has been applied since 1975 in the National Institute of Neurosurgery, Budapest. The intracavital treatment was only one among several applied treatment forms. In all patients a partial removal of the tumour has also been performed. The possibilities of evaluation of the effectiveness of the internal cyst irradiation are therefore limited. In most cases the intracavital treatment resulted in shrinkage of the cyst, or even was followed by its practical disappearence and the condition of the patients shows a decisive improvement. The growth of solid tumour parts is not influenced by this kind of treatment. Therefore the clinical improvement of the patient's condition depends also on the ratio between cyst and solid tumour volume. The optic nerve impairment did not improve in all cases. As a side-effect an oculomotor nerve paresis developed in several patients. Its possible explanations have been discussed, including lasting damage from tumour pressure.

Adolescent↗
PubMed1985

Migration and colonization of leukemic lymphoblasts in AKR and HSS inbred mice followed by serial enzyme determinations.

After transplantation of AKR and HSS leukemic cells into AKR and HSS inbred mice as well as into their hybrids, the distribution and proliferation of the cells depend on the host organism. The energy production and glycolytic enzyme activity of the settled cells differ from that of the injected leukemic cells. It may be supposed that either the cell transplantation was carried out with a heterogeneous cell population or the cells of the host organism started to dedifferentiate.

Animals↗
PubMed1982

Transplacental effects of carcinogens and non-carcinogens on activities of pyruvate kinase and lactate dehydrogenase as well as isozymic pattern of LDH in mouse lung.

The carcinogens, urethane (URTH), 3-methylcholanthrene (MCA) and dimethylnitrosamine (DMN) given to pregnant mice enhanced permanently the activities of pyruvate kinase (PK) and lactate dehydrogenase (LDH) in the lungs of offspring even well before the appearance of lung tumours. The noncarcinogenic analogues phenylurethane (PHUR) and pyrene (PYR), had no effect on PK or LDH activity. The non-carcinogenic pulmonary toxicant Paraquat (PAR) elicited only a temporary elevation in the activities of the enzymes tested. The H:M ratio of LDH sub-units in the lung tissue was permanently decreased by URTH administered transplacentally. PAR caused only a temporary decrease in the H:M ratio, while PHUR had no effect on the isozymic pattern of LDH.

Animals↗
PubMed1981

Regulation of glycolysis and oxygen consumption in lymph-node cells of normal and leukaemic mice.

Lymph-node cells of (AKR X C3H) F1 leukaemic mice showed a considerable increase of glycolytic activity and O2 consumption. The glycolytic enzymes phosphofructokinase, pyruvate kinase, aldolase and lactic acid dehydrogenase showed increased activities in leukaemic conditions. Studies on permeabilized leukaemic and normal lymph-node cells, and assays on partially purified phosphofructokinase and pyruvate kinase enzymes, revealed that the enhanced glycolysis of the tumour cells was due to the predominance of glycolytic isoenzymes relatively insensitive to the natural metabolic inhibitors. The glycolytic enzyme hexokinase showed decreased activity in leukaemic conditions, owing to a subcellular translocation of its bulk from the cytosol to the mitochondrial fraction. Association of hexokinase with the mitochondria accounted for an ATPase-like stimulatory action on cell respiration which can explain the increased O2 uptake of leukaemic cells.

Adenosine Triphosphate↗