Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aneuploidy is a characteristic of the majority of human cancers, and recent studies suggest that defects of mitotic checkpoints play a role in carcinogenesis. MAD1L1 is a checkpoint gene, and its dysfunction is associated with chromosomal instability. Rare mutations of this gene have been reported in colon and lung cancers. We examined a total of 44 cell lines (hematopoietic, prostate, osteosarcoma, breast, glioblastoma and lung) and 133 fresh cancer cells (hematopoietic, prostate, breast and glioblastoma) for alterations of MAD1L1 by RT-PCR-SSCP and nucleotide sequencing. Eight mutations consisting of missense, nonsense and frameshift mutations were found, together with a number of nucleotide polymorphisms. All the alterations in cell lines were heterozygous. Frequency of mutations was relatively high in prostate cancer (2/7 cell lines and 2/33 tumor specimens). We placed a mutant truncated MAD1L1, found in a lymphoma sample, into HOS, Ht161 and SJSA cell lines and found that it was less inhibitory than wild type MAD1L1 at decreasing cell proliferation. Co-expression experiments showed that the mutant form had a dominant-negative effect. Furthermore, this mutant impaired the mitotic checkpoint as shown by decreased mitotic indices in HOS cells expressing mutant MAD1L1 after culture with the microtubule-disrupting agent, nocodazole. Our results suggest a pathogenic role of MAD1L1 mutations in various types of human cancer.
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PMID:Mutations in the mitotic check point gene, MAD1L1, in human cancers. 1142 79

Eradicative levels of antitumor activity by cytokines and leukocytes have not yet been reached experimentally and are needed clinically. Only a limited number of human cancers respond to therapy with interferon (IFN), other cytokines, or mononuclear leukocytes despite significant antitumor activity in vitro. We studied the IFN and monocytic cell conditions that would lead to an eradicative effect using human cells in vitro. Targets of the IFN-activated monocytic cells were either four human tumor cell lines (human osteosarcoma [HOS], LOX melanoma, A549 lung tumor, and SNB-19 glioblastoma) or two diploid cell lines (WI38 and MRC5). An average of 30-90 colony-forming tumor target cells were cultured overnight in 96-well tissue culture plates prior to treatment with serially diluted IFN with or without activated elutriation-purified monocytes or lymphocytes. The target cell colonies were treated for 3 days. The colonies were then stained with crystal violet to determine the levels of antitumor activity. IFN-activated human monocytes reached an eradicative level (95%-100%) against three of four tumor cell lines. The eradicative level (1) was induced best in human monocytes activated by combined type I and II IFNs, (2) was effective against tumor cells that were growing for 24 h, (3) was specific for human tumors, as diploid human cells were not inhibited, and (4) required contact between the macrophage and the tumor cells. Also, for the first time, the minimal effective concentration (MEC) of IFNs to activate monocytes can approach those needed for antiviral activity. To our knowledge, this is the first report of near total eradication of many tumor cells, but not diploid cells, by IFN-activated monocytes. Because of its potency and specificity, the IFN-activated monocyte arm of the innate immune system may be a candidate for therapy of established tumors.
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PMID:Clinical model: interferons activate human monocytes to an eradicative tumor cell level in vitro. 1731 43

Tanapoxvirus (TPV) is a member of the genus Yatapoxvirus in the family Poxviridae and is endemic to equatorial Africa. This disease is restricted to human and non-human primates, producing a mild febrile illness characterized by a single or more rarely additional pock-like lesions on the extremities. While there are several studies elucidating the replication cycle and host range of TPV, there is currently no standardized investigation comparing the ability of TPV to successfully replicate in a variety of tumor cell lines. This study examined the cytopathic effect and calculated the efficiency of TPV replication in vitro using 14 different human cancer cell lines. TPV replicates efficiently in some human tumor cells, and is restricted in others when measured by viral titer at 7 days post infection. Results described here clearly demonstrate that TPV replication in one glioblastoma cell line (U-373), and one colorectal cancer cell line (HCT-116) is more productive than in owl monkey kidney cells (OMK). Replication in two renal cancer cell lines (ACHN and Caki-1) is also increased when compared to OMK. TPV infection produced the greatest change in cellular morphology in U-373 cells, and to a much lesser degree in the breast cancer cell lines T-47D and MCF-7, and in the ovarian cancer line SK-OV3. Negligible change was noted in glioblastoma line U-87, breast cancer line MDA-MB-435, osteosarcoma line HOS, melanoma line SK-MEL5, colorectal cancer line COLO205, and prostate cancer line PC3. The cell lines least permissive to TPV replication were the glioblastoma (U-87) and melanoma (SK-MEL5) cell lines.
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PMID:Differential susceptibility of human cancer cell lines to wild-type tanapoxvirus infection. 2046 Dec 27