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

We present a case of fetal glioblastoma which appeared after 28 weeks' gestation. The first ultrasonographic finding was an enlarged fetal head with right shifted falx cerebri at 31 weeks' gestation. At 33 weeks, a large and high echogenic mass in the left hemisphere and right enlarged ventricle was identified. Magnetic resonance imaging showed that the tumor was localized in the left hemisphere and a margin of the tumor was defined. Because fetal well-being judging from biophysical parameters was good and we considered that the tumor was resectable, a male fetus weighing 2,670 g was delivered at 34 weeks' gestation by cesarean section. However, he was inoperable due to consumptive coagulopathy and rapid growth of the tumor, and died on the 41st day of life.
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PMID:Fetal glioblastoma: rapid growth during the third trimester. 993 15

Protein kinase C alpha (PKC-alpha) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-alpha that reduces PKC-alphain human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this phase 2 study, aprinocarsen was administered to patients with recurrent high-grade gliomas by continuous intravenous infusion (2.0 mg/kg/day for 21 days per month). Twenty-one patients entered this trial. Their median age was 46 years (range, 28-68 years), median Karnofsky performance status was 80 (range, 60-100), median tumor volume was 58 cm3 (range, 16-254 cm3), and histology included glioblastoma multiforme (n = 16), anaplastic oligodendroglioma (n = 4), and anaplastic astrocytoma (n = 1). The number of prior chemotherapy regimens included none (n = 3), one (n = 10), and two (n = 8). No tumor responses were observed. Patients on this therapy rapidly developed symptoms of increased intracranial pressure with increased edema, enhancement, and mass effect on neuroimaging. The median time to progression was 36 days, and median survival was 3.4 months. The observed toxicities were mild, reversible, and uncommon (grade 3 thrombocytopenia [n = 3] and grade 4 AST [n = 1]), and no coagulopathy or CNS bleeding resulted from this therapy. Plasma concentrations of aprinocarsen during the infusion exhibited significant interpatient variability (mean = 1.06 mug/ml; range, 0.34-6.08 mug/ml). This is the first study to use an antisense oligonucleotide or a specific PKC-alpha inhibitor in patients with high-grade gliomas. No clinical benefit was seen. The rapid deterioration seen in these patients could result from tumor growth or an effect of aprinocarsen on bloodbrain barrier integrity.
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PMID:Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas. 1570 Dec 80

Activation of stromal response pathways in cancer is increasingly viewed as both a local and systemic extension of molecular alterations driving malignant transformation. Rather than reflecting passive and unspecific responses to anatomical abnormalities, the coagulation system is a target of oncogenic deregulation, impacting the role of clotting and fibrinolytic proteins, and integrating hemostasis, inflammation, angiogenesis and cellular growth effects in cancer. These processes signify, but do not depend on, the clinically manifest coagulopathy and thrombosis. In this regard, the role of driver mutations affecting oncoprotein coding genes such as RAS, EGFR or MET and tumour suppressors (PTEN, TP53) are well described as regulators of tissue factor (TF), protease activated receptors (PAR-1/2) and ectopic coagulation factors (FVII). Indeed, in both adult and pediatric brain tumours the expression patterns of coagulation and angiogenesis regulators (coagulome and angiome, respectively) reflect the molecular subtypes of the underlying diseases (glioblastoma or medulloblastoma) as defined by their oncogenic classifiers and clinical course. This emerging understanding is still poorly established in relation to the transforming effects of non-coding genes, including those responsible for the expression of microRNA (miR). Indeed, several miRs have been recently found to regulate TF and other effectors. We recently documented that in the context of the aggressive embryonal tumour with multilayered rosettes (ETMR) the oncogenic driver miR (miR-520g) suppresses the expression of TF and correlates with hypocoagulant tumour characteristics. Unlike in adult cancers, the growth of pediatric embryonal brain tumour cells as spheres (to maintain stem cell properties) results in upregulation of miR-520g and downregulation of TF expression and activity. We postulate that oncogenic protein and miR coding genes form alternative pathways of coagulation system regulation in different tumour settings, a property necessitating more personalised and biologically-based approaches to anticoagulation.
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PMID:Biological basis of personalized anticoagulation in cancer: oncogene and oncomir networks as putative regulators of coagulopathy. 2706 76

There are emerging linkages between biological and genetic aspects of cancer progression and the mechanisms of cancer-associated thrombosis. It is argued that reciprocal influences between cancer cells, their associated vascular stroma, and the hemostatic system may shape the mechanism of coagulopathy. In this regard, glioblastoma multiforme offers a paradigm where the prevalent occurrence of local microthrombosis and peripheral venous thromboembolism can be linked to the profiles of oncogenic driver mutations and their impact on the expression of coagulation-related genes (coagulome). These relationships can be recapitulated in cellular models of glioblastoma, where the expression of tissue factor, podoplanin, and the release of procoagulant microparticles (extracellular vesicles) remains under the control of oncogenic pathways (epidermal growth factor receptor variant III, isocitrate dehydrogenase 1). These pathways define molecular subtypes of glioblastoma that express differential coagulomes. Moreover, single-cell sequencing of glioblastoma samples reveals a combinatorial rather than common profile of both subtype markers and coagulation-related genes. Based on these emerging observations, the authors suggest that cancers may operate as coagulant composites, where individual cells and their dominant populations express different procoagulant phenotypes, resulting in the net impact on the hemostatic system. They suggest that relating these mechanisms to clinical presentations of thrombosis may facilitate a more causality-based, personalized, and possibly cancer-specific thromboprophylaxis and treatment.
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PMID:Oncogenes and Clotting Factors: The Emerging Role of Tumor Cell Genome and Epigenome in Cancer-Associated Thrombosis. 3109 13