Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of intravascular malignant lymphomatosis (IML) presenting as progressive cerebral infarction is reported. A 62-year-old previously healthy male developed progressive dementia. MRI of the brain at the nearest hospital revealed multiple infarcts with unknown etiology. His level of consciousness deteriorated rapidly, and then he was transferred to our hospital for further evaluation. High grade fever, raised serum C reactive protein (CRP), and raised lymphoma markers (serum LDH and soluble IL-2 receptor (sIL-2R)) were observed. Repeated brain MRI disclosed progression of multifocal cerebral infarctions. We considered IML most likely, and we performed muscle biopsy. However muscle biopsy didn't demonstrate any proliferation of neoplastic cells of lymphoid origin within small vessels. Thereafter IML was diagnosed by brain biopsy. The patient underwent chemotherapy, but died of pneumonia due to severe myelosuppression. IML is a rare disease but most commonly shows neurological symptomatology as its clinical manifestation. Dementia is the most common neurological symptom, and progressive multiple infarction is the most common of the MRI findings. Rapidly progressive dementia associated with multiple infarction, when elevated CRP, LDH and sIL-2R are observed in the laboratory data, is suggestive of IML.
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PMID:[A case of intravascular malignant lymphomatosis presenting as cerebral infarction]. 1112 88

A 46-year-old woman with a previous diagnosis of sarcoidosis presented with morphologically typical large granular lymphocyte (LGL) leukemia/lymphoma with an aggressive clinical course. Epstein-Barr virus DNA was detected in peripheral blood mononuclear cells by PCR. The phenotype was typical of the T cell lineage (CD2+ CD3+ CD5+ CD7+ CD8+ TCRalphabeta+) but with the absence of the CD16, CD56, CD57 NK cell markers. In addition, the LGLs expressed CD122 (p75) in the absence of CD25 which is characteristic of LGLs. These leukemic LGLs did not exhibit NK activity. The clonal nature of this proliferation was demonstrated by the rearrangement of the TCRgamma gene. This phenotypically unusual but morphologically typical LGL leukemia/lymphoma may represent the clonal expansion of a minor normal subset of T-LGLs which do not express any NK cell markers, probably corresponding to in vivo activated T cells.
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PMID:Aggressive variant of morphologically typical T large granular lymphocyte leukemia/lymphoma lacking NK cell markers. 1115 85

Malignant lymphoma is a major cause of hemophagocytic syndrome (HPS), in which reactive macrophages, phagocytic red blood cells, white blood cells, and platelets proliferate in bone marrow, liver, and spleen. In contrast to T/NK-cell lymphoma-associated hemophagocytic syndrome (T/NK-LAHS), few cases of B-LAHS have been reported; thus, the clinical characterization of B-LAHS remains to be established. We describe here four cases of B-LAHS that include the following features: (1) HPS was the initial presentation; (2) bone marrow involvement with large-cell lymphomas was noted in all cases, despite lack of remarkable lymphadenopathy; (3) no active infection with Epstein-Barr virus as the etiological agent was confirmed; (4) except for the spleen in one case, primary site of lymphoma could not be determined; and (5) serum IL-6, soluble IL-2 receptor, and IFN-gamma- but not TNF-alpha and IL-1 beta-, were significantly elevated. Such characteristics are peculiar to and different from those usually seen in B-cell lymphoma, suggesting that B-LAHS is a unique clinical entity among B-cell lymphomas.
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PMID:[Clinical characterization of B cell lymphoma-associated hemophagocytic syndrome]. 1115 15

HTLV-I is causually related to the oncogenesis of adult T cell leukemia (ATL). However, the precise mechanism of HTLV-I oncogenesis is unclear. HTLV-I Tax protein functions as an activator of various cellular genes, including IL-2, IL-2 receptor-alpha, and c-fos through the activation of nuclear transfer factors such as NF-kappaB and SRF, and also potently activates trascription of viral genes through CREB/ATF sites in the viral LTR. However, Tax activation of HTLV-I infected T cells through the above pathways induces polyclonal proliferation of the cells in vitro; Tax however may function only transiently in the immediate post-infection period following infection in vivo. The long latent period of 60 years from infection to onset of disease suggests other mechanisms for ATL oncogenesis. Recent studies suggest that the malignant transformation of ATL is a multi-hit phenomena, suggesting that discrete genetic events are responsible for ATL oncogenesis. These genetic events could be responsible for the different stages of ATL: smoldering, chronic, lymphoma, and acute type, p16 and p53 genes are important negative regulators of the cell cycle and are often found to be mutated in neoplasms. Recent studies including ours demonstrated a high frequency of alteration of these two genes in primary ATL cells. Furthermore, alteration of the two genes is associated with acute but not chronic type ATL. In addition, p16 gene alteration is linked to the growth rate of ATL cells, suggesting that the alteration of these cell cycle regulatory genes may be related to progression from smoldering or chronic to acute or lymphoma type ATL. Tax may be involved in mutagenesis of these genes through suppression of DNA-beta polymerase gene expression during the process from latent period to acute/lymphoma type. Once transformation occurs, activation of the pathway between Tax and the three nuclear transfer factors, NF-kappaB, SRF, and CREB/ATF, contributes to establish the aggressive manifestations of acute/lymphoma type ATL cells.
Leuk Lymphoma 2001 Jan
PMID:HTLV-I Tax related dysfunction of cell cycle regulators and oncogenesis of adult T cell leukemia. 1142 48

This article focuses on the recent dramatic advances in the applications of monoclonal antibody therapy to hematopoietic and neoplastic disease. The increase in the understanding of the role of growth factors and their receptors in the pathogenesis of malignancy and other undesirable hematological events taken in conjunction with the ability to produce humanized chimeric monoclonal antibodies to these targets is providing a new perspective for the treatment of leukemia, lymphoma and breast cancer, autoimmune disease and for prevention of ischemic complications. Dr. Waldmann describes approaches targeting the Her2/neu and the II-2/IL-15 receptor systems. The Her2/neu receptor is overexpressed in select breast, ovarian, gastric and pancreatic neoplasms. The use of trastuzumab (Herceptin) in the treatment of patients with breast cancer whose tumors overexpress this receptor are reviewed. The IL-2 receptor (Tac) is expressed on select malignant cells (adult T cell leukemia, hairy cell leukemia) and activated T cells involved in autoimmune disease and organ rejection. Humanized anti-Tac alone (daclizumab, Zenapax) or armed with toxins or radionuclides have been used successfully in the treatment of leukemia. Dr. Levy updates the experience with rituximab targeting CD20 on B cell lymphomas and reviews the antibodies to CD3, CD22, CD33, CD52, HLA-DR beta chain and HLA-D currently in or proposed for clinical trials, including radiolabelled antibodies. In the last section, Dr. Coller reviews the therapeutic results achieved with abciximab (ReoPro), an antagonist of platelet receptor GPIIbIIIa for the prevention of restenosis in percutaneous coronary interventions and the treatment of unstable angina. The mechanism of action, pharmacology and safety and efficacy of abciximab are reviewed.
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PMID:Emerging Therapies: Spectrum of Applications of Monoclonal Antibody Therapy. 1170 53

Fusion proteins are recombinant molecules that combine a targeting mechanism to a cytocidal moiety. DAB(389)IL-2 (denileukin diftitox; ONTAK), with a unique mechanism of action, is the first genetically constructed fusion protein to reach the clinic. In this molecule, the interleukin-2 (IL-2) gene is genetically fused to the enzymatically active and translocating domains of diphtheria toxin. DAB(389)IL-2 is internalized into IL-2 receptor-bearing cells by endocytosis. The ADP-ribosyltransferase activity of diphtheria toxin is cleaved in the endosome and is translocated into the cytosol where it inhibits protein synthesis, leading to apoptosis. DAB(389)IL-2 and its predecessor, DAB(486)IL-2, have shown clinical activity in a variety of diseases, including B-cell non-Hodgkin's lymphoma, cutaneous T-cell lymphoma (CTCL), Hodgkin's disease, psoriasis, rheumatoid arthritis, and HIV infection. The highest response rates were observed in CTCL, and this became the focus of clinical trials leading to its subsequent approval by the United States Food and Drug Administration for this disease. The potential applications of DAB(389)IL-2 in lymphomas are reviewed.
Clin Lymphoma 2000 Sep
PMID:DAB(389)IL-2 (ONTAK): a novel fusion toxin therapy for lymphoma. 1170 18

Genetic engineering has led to the development of fusion protein toxins, which are targeted effector molecules that combine a targeting ligand such as a growth factor with a cytocidal moiety such as a plant or bacterial toxin. The first genetically constructed family of fusion proteins used diphtheria toxin as the toxophore for receptor-binding domain substitution. Diphtheria toxin consists of three domains: an enzymatically active adenosine diphosphate (ADP) ribosyltransferase domain, a hydrophobic transmembrane domain, and a C-terminal receptor-binding domain. Introduction of the enzymatically active domain into the cytosol via receptor-mediated endocytosis results in inhibition of protein synthesis by ADP ribosylation of elongation-factor 2. DAB(486)IL-2, in which the native receptor-binding domain of diphtheria toxin was replaced with the full-length interleukin-2 (IL-2) gene, was capable of intoxicating high-affinity IL-2 receptor-bearing cells in vitro with an IC(50) of 10(-10) M; whereas, cells lacking the full component of the high-affinity IL-2 receptor (p55, p75, p64) were relatively resistant (IC(50) of 10(-8) M). Because of a short in vivo half-life of DAB(486)IL-2, efforts to reengineer the molecule were undertaken, leading to the DAB(389)IL-2 construct, which had a twofold to threefold higher Kd than DAB(486)IL-2 and a longer half-life, resulting in a tenfold increase in potency. Thus far, the clinical activity of both IL-2 chimeric fusion toxins has been similar, with the DAB(389)IL-2 molecule displaying more favorable pharmacokinetics.
Clin Lymphoma 2000 Nov
PMID:DAB(389)IL-2 (denileukin diftitox, ONTAK): a new fusion protein technology. 1170 60

We report on an elderly patient with a malignant lymphoma forming a huge mass in the heart. An 82-year-old woman became aware of general fatigue and a cough in August 1999. Her right supraclavicular, bilateral axillary, and right inguinal lymph nodes were swollen. A hypodermical mass in the right frontal chest was detected. Her left axillary lymph node was biopsied. She was diagnosed as having non-Hodgkin lymphoma, diffuse large cell type, B-cell type. Computed tomography scans showed a markedly thickened right ventricular wall of the heart, swollen lymph nodes of the mediastinum, bilateral pleural effusions, and a tumor in the spleen. Lymphoma cells were found in the pleural effusion, and the lymphoma was diagnosed as clinical stage IV. Hypofunction of the heart, ejection fraction (EF) 49%, was demonstrated with transthoracic echocardiography. EF increased to 70% after 3 courses of chemotherapy with CHOP regimen. All lesions disappeared after 6 courses of chemotherapy were completed. After consolidative radiotherapy with a total dose of 37 Gy to the mediastinum and heart, bilateral pleural effusions, elevation of the patient's lactate dehydrogenase level and soluble IL-2 receptor value were recognized, which suggested relapse of the lymphoma, although histopathological confirmation could not be realized.
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PMID:[An elderly non-Hodgkin lymphoma patient with a massive tumor of the heart]. 1222 22

Angiocentric immunoproliferative lesion (AIL) is the angiocentric and angiodestructive process of lymphoreticular cells with vascular invasion. AIL of the lung is rare. We treated a 57-year-old woman with AIL of the lung in whom chest radiography and computed tomography showed ground-glass opacity in the left lower lobe and lingular segment. Since macroscopical and intraoperative lung biopsy findings could not rule out the possibility of malignancy, including malignant lymphoma, we conducted left pneumonectomy. Immunohistological examination of the tumor showed that infiltrating lymphocytes consistent with AIL. Because tumor markers such as serum LDH and soluble IL-2 receptor increased postoperatively, we conducted systemic chemotherapy, after which elevated serum tumor markers decreased.
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PMID:Angiocentric immunoproliferative lesion of the lung. 1222 22

The development of central pontine myelinolysis (CPM) has rarely been reported in association with hemophagocytic syndromes (HPS). Here we report a unique case of Epstein-Barr Virus (EBV)-related HPS which was accompanied with CPM. A 72-year-old man who had no significant medical history was admitted to our hospital due to high fever and progressing dysphasia and dysarthria. Physical examination revealed anisocoria of the right pupil, fixed reaction to light, and paralysis of the left vagus nerves. Magnetic resonance imaging revealed low signal intensity on T1-weighted images and high signal intensity T2-weighted images in the patient's central midpontine lesion. Initial work-up showed anemia and thrombocytopenia with elevated levels of serum ferritin, lactate dehydrogenase, and soluble IL-2 receptor. Bone marrow aspiration revealed hemophagocytosis. The EBV genome was detected in the peripheral blood using the polymerase chain reaction method. He was diagnosed as having EBV-related HPS and CPM. Despite intensive treatment with methylpredonisolone, immunoglobulin, and etoposide, he died due to progressive disease and fungal septicemia. The etiology and relation between CPM and HPS are discussed.
Leuk Lymphoma 2002 Oct
PMID:EBV associated hemophagocytic syndrome accompanied by central pontine myelinolysis. 1248 7


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