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)

An investigation of the usefulness of a segregating stock of nude mice [AF nude mice (AF-nu)] for screening anticancer agents was undertaken. The toxicity of anticancer agents, takes and growth rates of human tumour xenografts and chemosensitivities of xenografts in AF-nu were studied and compared with those in BALB/cA nude mice (BALB/cA-nu). The results showed differences in the pattern of mortalities of AF-nu and BALB/cA-nu administered a range of anticancer agents. Body weight changes in the two nude mouse strains differed in the case of 5-fluorouracil, but not for nimustine, adriamycin and vincristine. All tumours transplanted in AF-nu grew as in BALB/cA-nu. Growth rates of 2 xenografts (gastric cancer and glioblastoma) were not significantly different between the 2 nude mouse strains, but those of 2 lung tumour xenografts were significantly greater in AF-nu than those in BALB/cA-nu. There were no significant differences in chemosensitivities of human tumours in AF-nu and BALB/cA-nu (consistency rate as evaluated by our criteria was 88%). From these results, it is suggested that AF-nu are more suitable for anticancer agent screening and experimental chemotherapy of human tumour xenografts than BALB/cA-nu because of lower costs and high reproductive rate. Although they are genetically heterogeneous, sets of experimental animals sharing the same gene pool can be produced routinely.
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PMID:Toxicity of anticancer agents, growth and chemosensitivity of human tumour xenografts in a segregating stock of AF nude mice. 175 95

A combination of multiple primary neoplasm (MPN) with glioblastoma and cancer of other organs is extremely rare but might be spurred up in the field of neurosurgery because of increasing number of cured patients from cancer or malignant brain tumor. Four such cases are presented. Two of them are of heterochronous occurrence of tumors. One has survived for 17 years after treating four malignancies: uterus, stomach, breast cancer and glioblastoma multiforme in this order and free of brain tumor for 4 years. The other has survived 18 years after three malignancies: uterus, stomach cancer and glioblastoma but is in morbid neurological state for a year. A case of synchronous primary tumors is a combination with glioblastoma and maxillary cancer and the patient died of brain tumor after 4 years and two months. The other case is an old man with glioblastoma and stomach cancer but died of severe general and neurological condition for three months before treatment was started. The pathogenesis of MPN is unknown. Regarding intrinsic factors, heredity, age, genetic or immunological state have been proposed for possible mechanism of the synchronous occurrence of MPN. While extrinsic factors such as environmental changes due to irradiation or chemical exposure to host might also be important for heterochronous MPN. Discussions based on these cases and literature were also made on the biological nature and clinical characteristics of MPN malignant brain tumor combined with cancer of other organs.
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PMID:[Multiple primary neoplasm--glioblastoma combined with cancer of other organs]. 282 47

Activities of pyrimidine nucleoside phosphorylase in brain tumors were measured and their relationship to a clinical course of the patients was investigated. Pyrimidine nucleoside phosphorylase is said to exist more quantitatively in malignant tumors such as Sarcoma 180, Ehrlich ascites carcinoma, Walker 256, and hepatoma, and very little in normal tissues. In brain tumors the activities were measured by bioassay and compared to that of Sarcoma 180. When the activity of Sarcoma 180 was expressed to be 100%, those of brain tumors were as follows: ten cases of normal brain less than 8.5; six cases of glioblastoma 39.3 +/- 30.7; five cases of astrocytoma 22.0 +/- 13.8; five cases of meningioma 22.4 +/- 13.7; two cases of oligodendroglioma 8.1 and 11.3; two cases of sarcoma 94.3 and 145.4; chordoma 48.0; ependymoblastoma 3.7; plexus papilloma 22.5; parotid cancer 43.4; ten cases of metastatic brain tumors from lung cancer 61.5 +/- 41.6; two cases from breast cancer 28.0 and 68.8; that from thyroid cancer 10.0; that from gastric cancer 13.5; malignant melanoma 77.2. In 12 cases of gliomas (glioblastoma, astrocytoma, oligodendroglioma) the mean activity was highest in glioblastoma (39.3), followed by astrocytoma (22.0) and oligodendroglioma (9.7). The postoperative survival time became shorter in gliomas with the higher activities. In metastatic brain tumors from lung, breast, and gastric cancer, the average time from the diagnosis of primary cancer to brain metastasis was shorter in cases with high activities and longer in cases with low activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activities of pyrimidine nucleoside phosphorylase in brain tumors and antitumor effect of 5'-DFUR]. 622 41

Previously, we identified an amplified gene in a stomach cancer cell line, KATO-III, and designated it K-sam. This gene was later found to be identical with a gene for a receptor tyrosine kinase, bek/FGFR2. One of the characteristics of the K-sam gene is structural diversity of its transcripts; K-sam complementary DNA (cDNA) cloned from human brain (K-sam-I) has a completely different sequence at the third extracellular immunoglobulin-like domain as compared to that of the K-sam cDNA derived from KATO-III cells (K-sam-II). Recent study has revealed that this difference signifies a differential ligand affinity; the receptor encoded by the K-sam-I cDNA has a high affinity for basic fibroblast growth factor (bFGF), while the K-sam-II cDNA corresponds to a receptor with the high affinity for keratinocyte growth factor (KGF). Reverse transcription-polymerase chain reaction and RNA blot analysis showed that the K-sam-II-type transcript was present in carcinoma cell lines but not in any of the sarcoma cell lines examined. The K-sam-I-type transcript was expressed in both carcinoma and sarcoma cell lines. Furthermore, KGF enhanced the DNA synthesis of the esophageal cancer cells, TE-1, in a dose-dependent manner, while the effect of bFGF was not substantial. In contrast, the glioblastoma cell line, A-172, that expressed the bFGF receptor showed a mitogenic response to bFGF but not to KGF. These data suggest that KGF is a growth factor used preferentially in cancer cells, and this preference is based on the presence of the K-sam-II-type receptor in carcinoma cells but not in sarcoma cells due to alternative splicing.
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PMID:Preferential expression of the third immunoglobulin-like domain of K-sam product provides keratinocyte growth factor-dependent growth in carcinoma cell lines. 827 90

Cytotoxic activity of sodium ascorbate against a human glioblastoma T98G cell line was concentration-dependently inhibited by serum in the RPMI1640 medium. The inhibitory effect of sera from pancreatic or stomach cancer patients was significantly higher than that of fetal bovine serum (FBS), with or without heat-inactivation. The cytotoxic activity of sodium ascorbate almost completely disappeared in 60-80% of patient sera. ESR spectroscopy revealed that both patient sera and FBS increased the ascorbyl radical intensity, but to significantly lower extents, as compared with that attained by RPMI1640 medium. The present study suggests the importance of re-evaluating the efficacy of not only ascorbate but also other chemotherapeutic drugs under more physiological conditions.
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PMID:Inhibition of cytotoxic activity of ascorbate by human cancer patient sera. 906 88

Although CTLs bear main immune responses in human tumors, stable CTL clones against human lung cancer have rarely been generated. Our previous study demonstrated efficient autologous CTL induction in human gastric cancer and glioblastoma by cytokine combination of interleukin (IL)-1beta (167 IU/ml), IL-2 (67 IU/ml), IL-4 (67 IU/ml), and IL-6 (134 IU/ml). In this study, we demonstrated successful induction of autologous stable CTLs in five of six patients with lung adenocarcinoma from mixed-lymphocyte tumor culture using this cytokine combination. All CTLs revealed potent and specific killing activity against autologous target cells (over 75% in CD8+ CTLs and over 50% in CD4+ CTLs at an E:T ratio of 10 for 24 h). Using a series of antibodies, CD8+ CTLs showed to recognize tumor-specific antigens of lung cancer cells through HLA class I. In the separate experiments, failure of CTL induction from monocyte-depleted peripheral blood mononuclear cells and appearance of cells with characteristics of dendritic cells from adherent peripheral blood mononuclear cells in the culture of the same concentration of IL-1beta, IL-4, and IL-6 indicated that CTLs can be efficiently generated by this cytokine combination via possible dendritic cell induction. This is the first study of an efficient and reproducible in vitro CTL induction against human lung cancer.
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PMID:Autologous high-killing cytotoxic T lymphocytes against human lung cancer are induced using interleukin (IL)-1beta, IL-2, IL-4, and IL-6: possible involvement of dendritic cells. 1035 58

Secreted glycoprotein WNTs play important roles in carcinogenesis and development. We have previously reported molecular cloning of WNT-2B/WNT-13. Here, we have isolated a novel WNT-2B isoform (WNT-2B2), in addition to the original WNT-2B isoform (WNT-2B1). WNT-2B1 and WNT-2B2 are completely different in the 5'-UTR and in the N-terminal part of the coding region. The N-terminal hydrophobic domain is contained in WNT-2B1, but not in WNT-2B2. WNT-2B1 and WNT-2B2 share the WNT-core domain, and show 87.0% amino-acid identity. We have determined the structure of the WNT-2B gene. The WNT-2B1 mRNA consists of exons 1, 2, and 4-7, while the WNT-2B2 mRNA consists of exons 3-7. WNT-2B2 was expressed in fetal brain, fetal lung, fetal kidney, caudate nucleus, testis, glioblastoma cell lines A172, SW1783, gastric cancer cell lines MKN28, MKN74, and cervical cancer cell line HeLa S3. WNT-2B1 expression level was relatively higher in fetal brain and fetal lung than in other tissues or cell lines expressing WNT-2B2. These results indicate that the WNT-2B1 and WNT-2B2 mRNAs are transcribed due to alternative splicing with distinct expression profile. This is the first report on the WNT isoforms derived from the same gene due to alternative splicing.
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PMID:Alternative splicing of the WNT-2B/WNT-13 gene. 1094 66

FMNL (NM_005892.2) is a 5'-truncated partial cDNA encoding a Formin-homology protein related to DAAM1, DAAM2, DIAPH1 and DIAPH2. Here, we identified three members of FMNL gene family in the human genome by using bioinformatics. FMNL1 gene, corresponding to 5'-truncated KW-13 and FMNL cDNAs, was located within reference genomic contig NT_010748.9 (nucleotide position 100576-125849, forward orientation). FMNL2 gene, corresponding to KIAA1902 and FHOD2 cDNAs, was located within NT_005151.10 (nucleotide position 122465-436828, forward orientation). FMNL3 gene, corresponding to 5'-truncated DKFZp762B245 and KIAA2014 cDNAs, was located within NT_026397.10 (nucleotide position 209769-279037, reverse orientation). FMNL1, FMNL2 and FMNL3 genes encode A and B isoforms with the C-terminal divergence due to alternative splicing (cassette splicing of exon 26). FMNL1A (1100 aa), FMNL1B (1114 aa), FMNL2A (1087 aa), FMNL2B (1093 aa), FMNL3A (1028 aa) and FMNL3B (1027 aa) consist of FDD, FH1 and FH2 domains. Total amino-acid identity were as follows: FMNL1A vs. FMNL2A, 59.3%; FMNL1A vs. FMNL3A, 56.1%; FMNL2A vs. FMNL3A, 68.6%. FMNL1 gene was mapped to human chromosome 17q21. FMNL2 gene was linked to FNBP3/HYPA gene on chromosome 2q23.3, while FMNL3 gene was linked to FNBP3L/HYPC gene on chromosome 12q13. FMNL1 mRNA was expressed in natural killer cells, Burkitt lymphoma, pancreatic cancer, prostate cancer, and lung large cell carcinoma, FMNL2 mRNA in several normal tissues, diffuse-type gastric cancer, breast cancer, chondrosarcoma, melanoma, and glioblastoma, and FMNL3 mRNA in gastric cancer. FMNL1, FMNL2 and FMNL3 might be implicated in polarity control, invasion, migration, or metastasis through regulation of the Rho-related signaling pathway.
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PMID:Identification and characterization of human FMNL1, FMNL2 and FMNL3 genes in silico. 1268 86

Marimastat [BB 2516, TA 2516] is a second-generation anticancer drug originally developed with British Biotech in Europe and North America. It is an orally active metalloprotease inhibitor of the same class as batimastat, and is the first compound in this class to have completed a pivotal clinical trial. Marimastat also has collagenase- and angiogenesis-inhibiting properties. British Biotech and Schering-Plough have signed an agreement enabling the latter to develop and market marimastat in North America and Europe. Under the terms of the agreement, British Biotech will receive an up-front license fee of 4 million US dollars and a 4 million US dollars equity investment in British Biotech by Schering-Plough. Schering-Plough holds rights to marimastat in all countries other than the Far East and Japan. The two companies are considering asking the FDA for accelerated approval in gastric cancer based on the secondary endpoint of progression-free survival. Marimastat is licensed to Tanabe Seiyaku in Japan, where phase II clinical trials are underway for the treatment of advanced gastric cancer and lung cancer. Further phase II trials in other tumour types are planned. The commencement of phase II trials in Japan resulted in a milestone payment of 5 million US dollars to British Biotech from Tanabe Seiyaku. Tanabe Seiyaku also holds rights to marimastat in the Far East. Marimastat has been in pivotal phase III trials in glioblastoma, breast, ovarian and small and non-small cell lung cancer, but these trials have all been discontinued because marimastat failed to show superior efficacy over either standard chemotherapy or placebo. Results from the marimastat 131 trial in patients with glioblastoma, for example, indicated that marimastat was no better than placebo at prolonging survival in these cancer patients. In June 2000, when the results of this study were released, shares in British Biotech fell 21.6% to just 19 pence per share. The phase III trial in small cell lung cancer was discontinued when the results of study 140 were released in February 2001 showing that marimastat was not significantly more effective than placebo in prolonging the survival of small cell lung cancer patients. The results of this study were consistent with those reported in study 117. British Biotech has also conducted a phase III placebo-controlled study of marimastat as monotherapy in patients with inoperable gastric cancer at 37 centres throughout Europe. Results from this trial indicated that it did not achieve its primary endpoint of a statistically significant survival benefit over placebo. However, data collected during the follow-up period have shown increases in survival benefit in the treatment group in addition to a significant improvement in disease-free progression, the secondary endpoint of the trial. Development of marimastat for this indication is ongoing. In May 2001, British Biotech reported data from an interim analysis of results from the remaining phase III study in pancreatic cancer (study 183) that showed no patient benefit for marimastat recipients compared with gemcitabine. However, these results did not meet stopping criteria and the study continues under the guidance of Schering-Plough. The multicentre trials are being conducted in the US, Canada and the European Union. The phase III trial of marimastat in combination with carboplatin that was being conducted in patients with ovarian cancer was discontinued because British Biotech realised that the design of the trial was insufficient for registration in the US or Europe. Altogether, seven phase III studies have failed to meet their primary end-points, but the company has stated that the effectiveness of marimastat is more likely to be seen in patients with less advanced disease. Phase II trials in prostate and head and neck cancer are still underway in the US.
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PMID:Marimastat: BB 2516, TA 2516. 1275 9

Hepatocyte growth factor/scatter factor-Met signaling has been implicated in tumor growth, invasion, and metastasis. Suppression of this signaling pathway by targeting the Met protein tyrosine kinase may be an ideal strategy for suppressing malignant tumor growth. Using RNA interference technology and adenovirus vectors carrying small-interfering RNA constructs (Ad Met small-interfering RNA) directed against mouse, canine, and human Met, we can knock down c-met mRNA. We show a dramatic dependence on Met in both ligand-dependent and ligand-independent mouse, canine, and human tumor cell lines. Mouse mammary tumor (DA3) cells and Met-transformed NIH3T3 (M114) cells, as well as both human and canine prostate cancer (PC-3 and TR6LM, human sarcoma (SK-LMS-1), glioblastoma (DBTRG), and gastric cancer (MKN45) cells, all display a dramatic reduction of Met expression after infection with Ad Met small-interfering RNA. In these cells, we observe suppression of tumor cell growth and viability in vitro as well as inhibition of hepatocyte growth factor/scatter factor-mediated scattering and invasion in vitro, whether Met activation was ligand dependent or not. Importantly, Ad Met small-interfering RNA led to apoptotic cell death in many of the tumor cell lines, especially DA3 and MKN45, but did not adversely affect MDCK canine kidney cells. Met small-interfering RNA also abrogated downstream Met signaling to molecules such as Akt and p44/42 mitogen-activated protein kinase. We further show that intratumoral infection with c-met small-interfering RNA adenovirus results in a substantial reduction in tumor growth. Thus, Met small-interfering RNA adenoviruses are reliable tools for studying Met function and raise the possibility of their application for cancer therapy.
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PMID:RNA interference reveals that ligand-independent met activity is required for tumor cell signaling and survival. 1552 Feb 3


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