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)

Two brothers developed multiple primary neoplasms in childhood; one had glioblastoma and non-Hodgkin's lymphoma at age 11 years, and the other brain tumor and acute leukemia at six years. A third brother died with myelogenous leukemia at thre years, and a fourth with cyanotic congenital heart disease at 11 weeks. Each child also had at least one hamartomatous lesion of the skin. The clinical features suggested von Recklinghausen's neurofibromatosis or other inherited cancer syndrome, but laboratory studies identified no markers of susceptibility to familial neoplasia.
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PMID:Double primary cancers in 2 young sibs, leukemia in another, and dextrocardia in a fourth. 19 73

A patient undergoing treatment with cytotoxic chemotherapy for Hodgkin's disease developed graft versus host disease (GVHD) following a transfusion of packed red cells. This is the 28th reported patient with a malignancy who did not have a bone marrow transplant and developed GVHD after transfusion of normal blood or blood products. All patients had received cytotoxic chemotherapy prior to acquiring GVHD. The underlying malignancies included lymphoma, acute leukemia, neuroblastoma, rhabdomyosarcoma, and glioblastoma. Twenty-three of the 28 patients died of GVHD. The incidence of transfusion-related GVHD in this patient population is low but the illness is often fatal as treatment is largely ineffective. Transfusion-related GVHD can be prevented by irradiating all blood products with 1500 rad prior to administration.
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PMID:Graft versus host disease following transfusion of normal blood products to patients with malignancies. 331 50

The effects of human interferon-beta (IFN-beta, MR-21) on the growth of xenografted human tumors in nude mice were examined. IFN-beta was administered to mice with malignant melanoma (SK-MEL-28 and Sk-14) intratumorally at a dose of 1 X 10(5)-3 X 10(5) IU/mouse, with acute leukemia (CCRF-HSB-2) intratumorally at a dose of 3 X 10(5) IU/mouse, with glioblastoma (U-373 MG) intravenously or intratumorally at a dose of 1 X 10(5)-6 X 10(5) IU/mouse, or with uterine cervical tumor (HeLa S3) intravenously at a dose of 0.3 X 10(5)-1 X 10(5) IU/mouse. IFN-beta inhibited the growth of all of these tumors in a dose-dependent manner.
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PMID:[Basic study on interferon-beta: Part IV. Antitumor effect on nude mouse-transplanted human tumors]. 371 59

The Shc gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are ubiquitously expressed and are downstream targets and effectors of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of Shc proteins in normal and transformed cells. In tumor cells with known TK gene alterations Shc proteins were constitutively phosphorylated and complexed with the activated TK. No constitutive Shc phosphorylation was found in primary cell cultures and normal tissues. In 14 of 27 tumor cell lines with no reported TK alterations, Shc proteins were constitutively phosphorylated and formed stable complexes with novel tyrosine-phosphorylated polypeptides. Ten distinct Shc-associated phosphoproteins were identified with molecular weights ranging from 30 to 200 kDa. In a subset of carcinoma cell lines, phosphorylated Shc proteins complexed with a p175 phosphoprotein that was identified as the constitutively activated EGFR. In one glioblastoma cell line, a Shc-associated p190 was identified as the activated PDGFR. In 13 of 14 acute leukemia samples phosphorylated Shc proteins were constitutively complexed with a p140 phosphoprotein. Some of the Shc-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that Shc proteins are common substrates of constitutively activated TKs and that the analysis of Shc phosphorylation allow the identification of tumors with constitutive TK activation.
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PMID:Constitutive phosphorylation of Shc proteins in human tumors. 767 49

The definition of radiation-induced tumors is based on indirect criteria. They were defined initially by Cahan: the tumors must occur at the irradiated site after a time of latency longer than 5 years and be of a different pathological type from the initially irradiated tumor. The central nervous system belongs to sensitive tissue and it seems that a threshold dose does not exist. Thus, the relative risk varies from 1.57 to 8.75 for a dose of 1 Gy. It increases with the time of observation with a maximum of 18.4 between 20 and 25 years. Thus the cerebral radiation-induced tumors would be dependent on low dose for large volumes of healthy cerebral tissue (tineas, acute leukemia), and high dose for small volumes as irradiated benign lesions (pituitary tumors, meningiomas). Several factors influence the incidence of these radiation-induced tumors, of which the age at exposure and individual susceptibility are related to heredity. To date, 3 cases of radio-associated glioblastoma and 5 cases of transformed vestibular schwannoma related to radiosurgery were reported in the literature. They do not present all the traditional criteria. Thus, we reported through our experience 2 cases illustrating these problems to confront them with the published data. The long-term risk of radiation-induced tumor requires a time of observation between 5 and 30 years. This risk is estimated at less than 1 per 1,000. It must be communicated to each patient and counterbalanced with the operational risk of a benign tumor (1 per 100 of perioperative mortality) or the hemorrhagic risk of an untreated arteriovenous malformation (1 per 100 per year).
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PMID:Radiosurgery and carcinogenesis risk. 1881 Feb 21

The non-random chromosomal translocations t(10;11)(p13;q23) and t(10;11)(p13;q14-21) result in leukemogenic fusion proteins comprising the coiled coil domain of the transcription factor AF10 and the proteins MLL or CALM, respectively, and subsequently cause certain types of acute leukemia. The AF10 coiled-coil domain, which is crucial for the leukemogenic effect, has been shown to interact with GAS41, a protein previously identified as the product of an amplified gene in glioblastoma. Using sequential synthetic peptides, we mapped the potential AF10/GAS41 interaction site, which was subsequently be used as scaffold for a library targeting the AF10 coiled-coil domain. Using phage display, we selected a peptide that binds the AF10 coiled-coil domain with higher affinity than the respective coiled-coil region of wild-type GAS41, as demonstrated by phage ELISA, CD, and PCAs. Furthermore, we were able to successfully deploy the inhibitory peptide in a mammalian cell line to lower the expression of Hoxa genes that have been described to be overexpressed in these leukemias. This work dissects molecular determinants mediating AF10-directed interactions in leukemic fusions comprising the N-terminal parts of the proteins MLL or CALM and the C-terminal coiled-coil domain of AF10. Furthermore, it outlines the first steps in recognizing and blocking the leukemia-associated AF10 interaction in histiocytic lymphoma cells and therefore, may have significant implications in future diagnostics and therapeutics.
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PMID:Characterization and inhibition of AF10-mediated interaction. 2469 30