Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bone marrow and/or peripheral blood from 126 patients with acute myeloid leukemia (AML), 57 with chronic myeloid leukemia (CML), 91 with acute lymphocytic leukemia (ALL), and 178 normal controls were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay to evaluate the association of the endostatin polymorphisms D104N (nucleotide 4349G --> A) with leukemia. In the 178 normal Taiwanese, the allele frequency of 4349G was 98% (348/356) and that of 4349A was 2% (8/356). The frequencies of homozygous 4349G (104D/D) and heterozygous 4349G/A (104D/N) were 95. 5% (170/178) and 4.5% (8/178), respectively. However, no individuals were homozygous 4349A (104N/N). Among the leukemia patients, 124/126 with AML (98.4%), 55/57 with CML (94.9%), and 89/91 with ALL (97.9%) were homozygous 4349G. In addition, 2/126 with AML (1.6%), 2/57 with CML (5.1%), and 2/91 with ALL (2.1%) were heterozygous 4349G/A. No patients were homozygous 4349A. Similar frequencies of endostatin polymorphisms were observed in leukemic patients and normal controls. This suggests that the endostatin polymorphism is not associated with the risk of leukemia.
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PMID:Assocation of endostatin D104N with leukemia. 1269 19

Antiangiogenic gene therapy offers an attractive approach to the treatment of a variety of malignancies, including those of the hematological system. However, evaluation of this approach has been hampered by the lack of appropriate animal models. We have recently produced transgenic mice expressing P230 bcr/abl that develop myeloproliferative disease (MPD) closely resembling human chronic myelogenous leukemia. Using this MPD murine model, we examined the feasibility of systemic antiangiogenic gene therapy for hematological malignancy. An adenoviral vector containing the secretable endostatin gene was injected into the right quadriceps muscle of the MPD mice. The increased endostatin level was detected for at least 6 months. Hematological parameters including platelet counts, granulocyte counts, and the hemoglobin concentration were improved by this gene therapy. Infiltration of megakaryocytes was also significantly inhibited in treated MPD mice. Reduction of the microvessel density was confirmed by histological examination. These results demonstrated, for the first time, that antiangiogenic gene therapy is effective to inhibit leukemogenesis caused by expression of the chimeric bcr/abl gene.
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PMID:Antiangiogenic gene therapy of myeloproliferative disease developed in transgenic mice expressing P230 bcr/abl. 1561 2

A better understanding of the biology and pathogenesis of hematological malignancies has led to the development of immunotherapeutic and immunoregulatory drugs. Many of these agents have revolutionized the current treatment modalities, while others are under investigation. Rituximab (anti-CD20 antibody) has been established as the gold standard of treatment for aggressive B-cell lymphomas in combination with CHOP and has shown significant activity as monotherapy in the treatment of indolent B-cell lymphomas. In follicular lymphomas the combination of Rituximab with chemotherapy improves the outcome compared to chemotherapy alone. CD 20-based radioimmunotherapy, with the advantage of the bystander effect, represents an additional therapeutic alternative in B-cell lymphomas and may produce tumor regression in Rituximab resistant patients. The anti-CD52 monoclonal antibody, alemtuzumab, further expands the armamentarium against lymphoid malignancies producing high response rates in these entities. Antibody-targeted chemotherapy such as gemtuzumab ozogamicin, consisting of an anti-CD33 antibody combined to calicheamicin, has shown efficacy in the treatment of refractory acute myeloid leukemia; exact indications, timing and dosing schedule for optimized efficacy remain to be determined. Interferons have proven significant activity in cutaneous lymphomas, hairy cell leukemia and chronic myelogenous leukemia by mechanisms that are not fully elucidated. Thalidomide, by acting as an immunomodulatory and antiangiogenic agent can modulate neoplastic cells microenvironment and lead to disease control in multiple myeloma as well as in numerous other hematological malignancies. Bortezomib, a proteasome inhibitor, displays significant anti-tumor activity, especially in multiple myeloma and lymphoproliferative disorders. The addition of these agents in therapeutic regimens has improved considerably the treatment of hematological malignancies.
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PMID:Immunotherapeutic and immunoregulatory drugs in haematologic malignancies. 1701 50