Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse model systems which allow bone marrow reconstitution can be used to analyse genetically programmed leukemia. The original and most widely used system is that of post 5-fluorouracil mouse hematopoietic stem cells (HSC) into lethally irradiated syngeneic mice. Another more recent system allows analysis of human HSCs in the NOD-SCID mouse. Both systems are discussed as models for analysis of gene induced leukemia.
Curr Med Chem Cardiovasc Hematol Agents 2003 Jun
PMID:Bone marrow reconstitution as a relevant model of genetically programmed leukemia. 1532 Jun 91

An 83-year-old man with chronic lymphocytic leukemia (CLL) for 10 years presented with dyspnea and hypotension. Blood investigations and electrocardiogram were consistent with acute myocardial infarction. The patient deteriorated quickly and died shortly thereafter. At autopsy, there was severe atherosclerosis of the coronary arteries and an inferolateral left ventricular wall myocardial infarct. Microscopy showed that CLL involved the nodes, liver, spleen, bowel, and kidneys. The coronary artery walls were infiltrated with leukemia cells invading the tunica media and the atheromatous plaque. Infiltration of the coronary arteries by CLL is not common and the possible role in coronary syndromes is discussed.
Cardiovasc Pathol
PMID:Chronic lymphocytic leukemia involving the coronary arteries with accompanying acute myocardial infarction. 1628 42

Arsenic trioxide is an effective treatment for patients with acute promyelocytic leukaemia (APL) who have relapsed from or are refractory to all trans-retinoic acid and anthracycline chemotherapy. Cardiac effects observed include electrocardiographic changes such as QTc prolongation, T-wave abnormalities, torsades de pointes and sudden death. We describe a case of a man, 76 years old, who was admitted to our department for dyspnoea in APL in treatment with arsenic trioxide. Chest radiograph illustrated an enlarged cardiac silhouette and bilateral pleuric effusion and the ECG evidenced QT prolongation. The patient was also submitted to transthoracic echocardiography that revealed moderate pericardial effusion without signs of cardiac tamponade and a normal biventricular function. This condition was considered to be associated with arsenic trioxide polyserosit and the drug therapy was immediately discontinued and steroid drugs started. After 2 weeks of arsenic trioxide therapy suspension there was evidence of complete resolution of pericardial and pleuric effusion and the ECG showed normal QT interval.
Cardiovasc Toxicol 2008 Mar
PMID:QT prolongation: a case of arsenical pericardial and pleural effusion. 1808 26

Intensified treatments with multi-drug regimens are responsible for the continuously increasing survival of children with acute lymphoblastic leukaemia. However, together with the widespread use of central venous lines, they are also considered the main risk factors for the growing number of thromboembolic complications in this population. The rate of thrombosis that was observed in 17 prospective studies was 5.2%. Due to the high survival rate, it is relevant to apply strategies to the long term survivors who overcome the disease but who experience thromboembolic complications. Specific treatment includes anticoagulants, especially unfractionated heparin and low molecular weight heparins, and thrombolytic drugs in few cases. Guidelines for the treatment of thrombosis in childhood only became available recently, but they do not include specific clinical subsets such as children with acute lymphoblastic leukaemia. The problems involved in scheduling thrombosis treatment in children with malignancy have recently been discussed, however the paper does not provide practical diagnostic schemes or treatment schedules. Some important questions regarding optimal prevention and treatment are still unanswered. Moreover, antithrombotic therapy in these patients is quite challenging owing to the higher risk of bleeding. We believe it would be possible to propose reasoned appropriate recommendations for treating thrombosis in children with acute lymphoblastic leukaemia, looking forward for the effects of recent patents. This paper is an attempt to provide a practical guide to the diagnosis and treatment of thrombotic events in children with acute lymphoblastic leukaemia, and it is aimed at physicians who have no specific knowledge of the diagnosis and management of thrombosis and haemostasis alterations in children.
Recent Pat Cardiovasc Drug Discov 2007 Jan
PMID:A practical approach to diagnosis and treatment of symptomatic thromboembolic events in children with acute lymphoblastic leukemia: recommendations of the "Coagulation Defects" AIEOP Working Group. 1822 Nov 3

Mediastinal granulocytic sarcoma (GS) is a relatively rare disease. We experienced a case of acute myeloid leukemia (AML) that took a rapid turn for the worse after the resection of a mediastinal GS. A healthy 60-year-old man had been in good general health all his life, but was diagnosed with a mediastinal tumor by his family physician and was referred to our department. The patient underwent resection of the mediastinal tumor because thymoma was highly suspected. On postoperative day (POD) 3, the patient suffered a fever as well as an elevated white blood cell (WBC) count and a high C-reactive protein level. His WBC count was 77,240 at its peak on POD 9, at which point the patient was diagnosed with AML by bone marrow aspiration. The immunohistological findings showed the features of leukemia, and GS was diagnosed. Despite chemotherapy, the patient died on POD 28 as a result of rapid disease progression.
Ann Thorac Cardiovasc Surg 2008 Jun
PMID:Resection of mediastinal granulocytic sarcoma triggered the rapid progression of acute myeloid leukemia. 1857 99

Angiogenesis is a complex process that is regulated by pro- and antiangiogenic factors. These factors can emanate from diverse sources including cancer cells, stromal cells, blood and extracellular matrix. Their relative contribution is likely to change with tumor type and tumor site. Vascular endothelial growth factor (VEGF) is now well confirmed as the primary and the most potent inducer of angiogenesis. To activate cellular signaling pathways, VEGF binds to receptor kinases VEGF-R1, R2 and R3. It then promotes several events required for the formation of new blood vessels, such as endothelial cell survival, proliferation, migration and vascular permeability. Activation of endothelial cells, leads to the secretion of enzymes which degrade the extracellular matrix (ECM) and hence promote metastasis. Similarly it promotes survival by inducing Bcl-2 expression on VEGF receptor positive leukemia. Besides being a potent mitogen for macrovascular cells derived from arteries, veins and lymphatics, it is also highly involved in a number of angiogenic related disorders including inflammatory diseases, rheumatoid arthritis, psoriasis, retinopathies and age related macular degeneration. Neovascularization and increased vessel permeability are being recognized as major causes of VEGF related pathogenesis. Therefore, inhibition of VEGF pathway is a strategy being widely pursued to provide new therapeutics for the treatment of VEGF related disorders. Over twenty compounds with anti-angiogenic properties ranging from VEGF neutralizing antibody, soluble receptors, receptor antagonists or tyrosine kinase inhibitors (TKIs) are either approved or are currently under clinical (phase I - III) study. This review aims to provide an updated account of how VEGF inhibitors are shaping up to become an important class of drugs used in the treatment of cancer.
Cardiovasc Hematol Agents Med Chem 2008 Oct
PMID:Inhibitors of vascular endothelial growth factor in cancer. 1885 47

Tumour cells are characterized by karyotype instability, which is accompanied by specific events in the chromatin structure and epigenetic patterns. Epigenetics involves heritable changes in the physical and biochemical state of chromatin, which have no effect on DNA sequences; therefore, changes in the nuclear radial arrangement of chromosomes can also be considered epigenetic events. Nuclear radial distributions of select genomic regions have been studied in many tumour cells and are not influenced by aberrations in chromosome number. On the other hand, genes involved in translocations take up new positions midway between the original coding sequences. The differentiation of leukaemia cells with clinically used agents is often accompanied by nuclear repositioning of tumour-related genes. However, the nuclear rearrangement is cell-type specific and not always associated with changes in the transcriptional activity. Similarly, cell type-specific chromatin structure is observed in tumour cells treated with select cytostatics and inhibitors of epigenetic processes, which have significant influences on the histone code. Chromatin structure and histone modifications were also affected by gamma radiation in leukaemia, multiple myeloma, and solid tumour cells. Interestingly, gamma radiation induced loci proximity, which has been suggested to increase the probability of exchange aberrations typically associated with tumour progression.
Cardiovasc Hematol Disord Drug Targets 2009 Mar
PMID:Chromatin structure and epigenetics of tumour cells: a review. 1927 77

New chemotherapeutic agents are still required to further optimise treatment of leukemia patients. Proteasome inhibition by bortezomib, PR-171 (carfilzomib) and NPI-0052 (salinosporamide A) has been successfully used for the treatment of multiple myeloma and mantle cell lymphoma and is considered also as novel treatment strategy in leukemia. Combination of proteasome inhibitors bortezomib and NPI-0052 induces synergistic anti-multiple myeloma activity both in vitro using multiple myeloma cells and in vivo in a human plasmacytoma xenograft mouse model. Cell death resulting from proteasome inhibition requires caspase activation and increased levels of reactive oxygen species. While bortezomib induces several caspases, NPI-0052 activates predominantly caspase-8-dependent pathway. We studied the effect of bortezomib (10 nM) on DNA synthesis and apoptosis in human acute myeloid cell lines KASUMI-1, ML-1, ML-2 and CTV-1 cells. Bortezomib was potent inhibitor of DNA synthesis in all four types of leukemia cells and induced apoptosis in KASUMI-1, ML-2 and CTV-1 cells but not in ML-1 cells. Other research groups showed that histone deacetylase inhibitors (valproic acid or benzamide derivative MS-275) in combination with NPI-0052 or PR-171 induced greater levels of acute leukemia cell death than in combination with bortezomib. Proteasome inhibition as monotherapy and its combination with many conventional therapies as novel treatment strategies in leukemia are promising. Malignant cells are more sensitive to this treatment than normal hematopoietic cells.
Cardiovasc Hematol Disord Drug Targets 2009 Mar
PMID:Antiproliferative and proapoptotic effects of proteasome inhibitors and their combination with histone deacetylase inhibitors on leukemia cells. 1927 78

The use of sublobar resection techniques (anatomic segmentectomy; extended wedge) in the treatment of early-stage non-small cell lung cancer has been associated with increased local recurrence rates compared with lobectomy. Recent data, however, have suggested that sublobar resection of smaller tumors (especially those < or =2 cm) can be performed with no significant difference in local recurrence or long-term survival. These findings have particular relevance in elderly patients and in those patients who may be at high risk for lobectomy because of underlying medical comorbidities. Careful patient selection on the basis of individualized assessment of specific patient and tumor characteristics will aid in selecting the optimal approach. For larger tumors, or when adequate surgical margins are not obtainable, lobectomy should be performed. Currently, active, prospective, randomized studies (Cancer and Leukemia Group B [CALGB] 140503 and American College of Surgeons Oncology Group [ACOSOG] Z4032) will provide critical insights in delineating the efficacy of sublobar resection techniques in early-stage non-small cell lung cancer.
Semin Thorac Cardiovasc Surg 2010
PMID:Sublobar resection for early-stage lung cancer. 2081 13

We made an attempt to evaluate the preventive effects of vanillic acid on isoproterenol-induced myocardial infarcted rats. Rats were pretreated with vanillic acid (5 and 10 mg/kg) daily for 10 days. After pretreatment, rats were injected with isoproterenol (100 mg/kg) at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol induction increased the activity of serum creatine kinase-MB and increased the levels of serum and heart cholesterol, triglycerides, free fatty acids in rats. It increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high-density lipoprotein cholesterol. Also, the activity of 3-hydroxy-3methyl glutaryl-coenzyme-A-reductase in the plasma and liver was increased, and lecithin cholesterol acyl transferase activity in the plasma and liver was decreased in isoproterenol-induced rats. Furthermore, isoproterenol-induced rats showed a decrease in myocardial expression of B-cell leukemia/lymphoma-2(bcl-2) gene and an increase in myocardial expression of bcl-2 associated-x (bax)-gene. Vanillic acid pretreated isoproterenol-induced rats positively altered all the above-mentioned biochemical parameters. Vanillic acid pretreatment also reduced myocardial infarct size in myocardial infarcted rats. In vitro study confirmed the potent free radical scavenging effect of vanillic acid. The observed effects are due to free radical scavenging effects of vanillic acid. This study may have a significant impact on myocardial infarcted patients.
Cardiovasc Toxicol 2011 Mar
PMID:Preventive effects of vanillic acid on lipids, bax, bcl-2 and myocardial infarct size on isoproterenol-induced myocardial infarcted rats: a biochemical and in vitro study. 2116 33


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