Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymidine labelling indices (LI) and the number of clonal chromosome aberrations were assessed in fine-needle aspirates from enlarged lymph nodes in 22 patients with non-Hodgkin's lymphoma (NHL). 11 patients had LI greater than 3.0 (median 8.4) and 11 others had LI less than 3.0 (median 1.0). Three categories of chromosome aberration were recorded: normal karyotype, 1-5 aberrations, and greater than or equal to 6 aberrations or multiple complex changes. The distribution of these categories was different among the patients with LI greater than 3.0 compared to those with LI less than 3.0 (p = 0.02). 8 of 11 patients with LI greater than 3.0 had greater than or equal to 6 or complex changes. The corresponding figures for patients with LI less than 3.0 were 2 out of 11. When 16 previously untreated patients were analysed separately, the median number of clonal aberrations was 6.5 in 8 patients with LI greater than 3.0 and 2.5 in 8 others with LI less than 3.0 (p = 0.025). The results suggest that early and spontaneous changes in the genetic material are common in lymphomas with a high proliferative activity. According to previous studies, therapeutic results are especially poor in NHL with high LI. It is proposed that a high proliferative activity of lymphoma cells facilitates an early development of several new mutants and that some of these may be resistant to chemotherapeutic agents.
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PMID:Proliferative activity and number of clonal chromosome aberrations in non-Hodgkin's lymphomas. 376 35

We studied antitumor effects of receptor tyrosine kinase inhibitor sunitinib (formerly SU11248) against a variety of hematologic malignancies including the following leukemias: eosinophilic (EOL-1), acute myeloid (THP-1, U937, Kasumi-1), biphenotypic (MV4-11), acute lymphoblastic (NALL-1, Jurkat, BALL-2, PALL-1, PALL-2), blast crisis of chronic myeloid (KU812, Kcl-22, K562), and adult T-cell (MT-1, MT-2, MT-4), as well as non-Hodgkin's lymphoma (KS-1, Dauji, Akata) and multiple myeloma (U266). Thymidine uptake studies showed that sunitinib was active against EOL-1, MV4-11, and Kasumi-1 cells, which possessed activating mutations of the PDGFRalpha, FLT-3, and c-KIT genes, respectively, with IC(50)s of <30 nmol/L. In addition, sunitinib inhibited the proliferation of freshly isolated leukemia cells from patients possessing mutations in FLT3 gene. Annexin V staining showed that sunitinib induced apoptosis of these cells. Sunitinib inhibited phosphorylation of FLT3 and PDGFRalpha in conjunction with blockade of mammalian target of rapamycin signaling in MV4-11 and EOL-1 cells, respectively. Interestingly, rapamycin analogue RAD001 enhanced the ability of sunitinib to inhibit the proliferation of leukemia cells and down-regulate levels of mammalian target of rapamycin effectors p70 S6 kinase and eukaryotic initiation factor 4E-binding protein 1 in these cells. Taken together, sunitinib may be useful for treatment of individuals with leukemias possessing activation mutation of tyrosine kinase, and the combination of sunitinib and RAD001 represents a promising novel treatment strategy.
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PMID:The antitumor effects of sunitinib (formerly SU11248) against a variety of human hematologic malignancies: enhancement of growth inhibition via inhibition of mammalian target of rapamycin signaling. 1704 Oct 96