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)

In 1986, we reported the discovery and isolation of a novel human herpesvirus (HBLV) from AIDS and other lymphoproliferative disorders. Because HBLV is distinct from other members of the herpesvirus family and can infect B- and T-lymphocytes and other human cells (megakaryocytes and glioblastoma cells), we suggested human herpesvirus-6 (HHV-6) as the taxonomic designation for this virus. In cultures from patients' peripheral blood, the evidence of HBLV can be recognized from the appearance of short-lived giant cells (2-10%), which are large, refractile, and are often mono- and binucleated. As these cells degenerate, extracellular virus particles are found in the culture medium. HBLV can infect fresh mononuclear cells, established B- and T-lymphoblastoid cell lines, megakaryocytes and glioblastoma cell lines. HBLV infection can be detected by: a. morphological changes; b. indirect immunofluorescence assay, in situ hybridization, southern blot analysis, polymerase chain reaction amplification; and c. electron microscopy. Because of its wide cell tropism, HBLV DNA sequences have been detected in B-cell lymphomas and short term cultured cells from Sjogren's patients. Expression of HBLV RNA was also detected in sarcoidosis. The etiological role of HBLV in human tumors is unclear. While in vitro data may not necessarily apply to in vivo conditions, the infection of various cell lines from tumors and fresh mononuclear cells suggests HBLV involvement in a variety of diseases.
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PMID:Utilization of human hematopoietic cell lines for the propagation and characterization of HBLV (human herpesvirus 6). 275 46

Although two-thirds of tumors occurring in the central nervous system (CNS) are primary neoplasms, only 10% of positive cerebrospinal fluid (CSF) specimens are from primary CNS tumors. In this study, we reviewed the cytologic findings of 21 positive CSF specimens from primary CNS tumors. A computer search identified 21 cases of positive CSF specimens from patients with primary CNS tumors from the archives. Follow-up included review of medical charts and histologic correlation. The specimens were from 20 patients (9 females and 11 males). Their ages ranged from 6-83 yr, old with a mean of 30 yr. The cases included 9 medulloblastomas, 7 gliomas (3 glioblastoma multiformes, 2 anaplastic astrocytomas, and 2 ependymomas), 2 germinomas, 2 non-Hodgkin's large B-cell lymphomas, and 1 ganglioneurocytoma. Two cases were classified as suspicious and the remaining as positive for malignancy. Immunocytochemistry was employed in 3 cases to support the cytologic diagnosis. These cases included one large-cell lymphoma (leukocyte-common antigen-positive), one germinoma (placental alkaline phosphatase-positive), and the ganglioneurocytoma (neuron-specific enolase- and synaptophysin-positive). There were no false-positive cases. Our results suggest that positive CSF cytology in patients with a primary CNS tumor is a reliable indicator of malignancy and reflects leptomeningeal involvement. The use of immunocytochemistry is helpful in confirming the cytologic impression in some cases.
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PMID:Cytology of primary central nervous system neoplasms in cerebrospinal fluid specimens. 1193 64

Diagnostically primary central nervous system lymphomas (PCNSL) have to be differentiated from glioblastoma and brain metastases. Histologically the overwhelming majority of PCNSL is represented by diffuse large B-cell lymphomas, in this series with a BCL6 expression in 80% of the cases detected by immunohistochemistry. Stereotactic biopsy is the method of choice in establishing the definite diagnosis and intraoperative smear cytology will detect the lymphoid blasts. To confirm the B-cell lineage, immunohistochemistry is needed (CD20, CD79a). Small reactive T-lymphocytes and monohistiocytic cells and activated "microglia" are found within and at the periphery of PCNSL foci. The infiltrated brain tissue shows partially pleomorphic reactive astrocytes that can be confused with neoplastic astrocytes, especially in small specimens. In contrast to high-grade gliomas, however, PCNSLs do not show endothelial proliferations. Subtypes or variants of diffuse large B-cell lymphomas can also be observed in cases of PCNSL: the anaplastic variant with large multinucleated tumour cells resembling Reed-Sternberg cells, T-cell rich B-cell lymphoma and intravascular B-cell lymphoma with primary manifestation within the brain or the spinal cord. HIV/AIDS-associated PCNSLs are characterised by large plasmoblastic or small Burkitt-like cells and tumour necrosis. Primary leptomeningeal large B-cell lymphomas do occur very rarely and are diagnosed by cerebrospinal fluid cytology.
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PMID:[Primary CNS lymphomas. Morphology and diagnosis]. 1218 81

Renal transplantation is method of choice for treatment of patients with end-stage renal disease without contraindications for immunosuppressive therapy. Neurological complications occur frequently in renal transplant recipients. They may be the consequence of immunosuppressive treatment, but more often evolve as the consequence of previous disturbances which developed during the state of uraemia and treatment with dialysis. The most pronounced neurotoxic effect has calcineurin inhibitors tacrolimus and cyclosporine. The spectrum of neurological disturbances caused by calcineurin inhibitors range from very mild symptoms as paraesthesiae, tremor, headache or flushing, to severe changes that may cause lethal outcome. Peripheral neuropathies in renal transplant recipients may occur in the form of mononeuropathy or polyneuropathy. Cerebrovascular diseases are consequence of changes on blood vessels caused by uraemia, dialysis and side effects of immunosuppressive drugs. They cause death in 8% of renal transplant recipients. Central nervous system (CNS) infections usually occur during the first posttransplant year. Unclear symptomatology frequently postpones the diagnosis. Diagnostic evaluation should include magnetic resonance imaging for localization of the process, as well as lumbal puncture in cases without contraindications for the procedure, in order to determine the causative agent. Regarding the ominous prognosis of CNS infections in the immunocompromised host, only timely diagnosis may improve survival. The most common causative agents are Cryptococcus neoformans, Listeria monocytogenes and Aspergillus funigatus. Viral infections also occur, and are commonly caused by herpes virideae, varicella-zoster virus and papova virus. CNS infections clinically present as meningitis, progressive dementia or focal neurological defect. The most common primary brain tumors are B-cell lymphomas, but glioblastoma, hemangioblastoma, leiomyosarcoma or glioma may also occur. In cases of neurological posttransplant complications, optimal treatment should be guided by neurologist, nephrologist and infectologist, in some cases also by neurosurgeons.
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PMID:[Neurological complications in renal transplant recipients]. 1857 36

Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase in the insulin receptor superfamily, was initially identified in constitutively activated oncogenic fusion forms - the most common being nucleophosmin-ALK - in anaplastic large-cell lymphomas, and subsequent studies have identified ALK fusions in diffuse large B-cell lymphomas, systemic histiocytosis, inflammatory myofibroblastic tumors, esophageal squamous cell carcinomas and non-small-cell lung carcinomas. More recently, genomic DNA amplification and protein overexpression, as well as activating point mutations, of ALK have been described in neuroblastomas. In addition to those cancers for which a causative role for aberrant ALK activity is well validated, more circumstantial links implicate the full-length, normal ALK receptor in the genesis of other malignancies - including glioblastoma and breast cancer - via a mechanism of receptor activation involving autocrine and/or paracrine growth loops with the reported ALK ligands, pleiotrophin and midkine. This review summarizes normal ALK biology, the confirmed and putative roles of ALK in the development of human cancers and efforts to target ALK using small-molecule kinase inhibitors.
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PMID:Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. 1927 11

MicroRNAs are aberrantly expressed in many cancers and can exert tumour-suppressive or oncogenic functions. As oncomirs promote growth of cancer cells and support survival during chemotherapy, thus microRNA-silencing therapies could be a valuable approach to be associated with anticancer drugs and chemotherapy treatments. miR-155 microRNA was found overexpressed in different types of cancer, such as leukaemias (PML, B-cell lymphomas), lung cancer and glioblastoma. GABA-A receptor downregulation was found correlated with glioma grading, with decreasing levels associated with higher grade of malignancies. A relationship between knock-down of miR-155 and re-expression of GABRA 1 protein in vivo was recently individuated. This finding has implication on the effectiveness of RNA-silencing approaches against miR-155 with the scope to control proliferation and signalling pathways regulated by GABA-A receptor. Applying microRNAs for treatment of brain tumours poses several problems, and fields to be solved are mainly the passage of the brain-blood barrier and the targeted delivery to specific cell types. Glioblastoma multiforme cells bud off microvesicles that deliver cytoplasmic contents to nearby cells. Thus, the exploitation of these mechanisms to deliver antagomir therapeutics targeting microvescicles in the brain could take the lead in the near future in the treatment for brain cancers in substitution of invasive surgical intervention.
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PMID:Potential of anti-cancer therapy based on anti-miR-155 oligonucleotides in glioma and brain tumours. 2283 37

Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.
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PMID:Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade. 2526 64

Mortality rates in patients diagnosed with central nervous system (CNS) tumors, originating in the brain or spinal cord, continue to remain high despite the advances in multimodal treatment regimens, including surgery, radiation, and chemotherapy. Recent success of adoptive cell transfer immunotherapy treatments using chimeric antigen receptor (CAR) engineered T cells against in chemotherapy resistant CD19 expressing B-cell lymphomas, has provided the foundation for investigating efficacy of CAR T immunotherapies in the context of brain tumor. Although significant efforts have been made in developing and translating the novel CAR T therapies for CNS tumors, including glioblastoma (GBM), researchers are yet to achieve a similar level of success as with liquid malignancies. In this review, we discuss strategies and considerations essential for developing robust preclinical models for the translation of T cell-based therapies for CNS tumors. Some of the key considerations include route of delivery, increasing persistence of T cells in tumor environment, remodeling of myeloid environment, establishing the window of treatment opportunity, harnessing endogenous immune system, designing multiple antigen targeting T cells, and rational combination of immunotherapy with the current standard of care. Although this review focuses primarily on CAR T therapies for GBM, similar strategies, and considerations are applicable to all CNS tumors in general.
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PMID:Strategies to Enhance the Efficacy of T-Cell Therapy for Central Nervous System Tumors. 3328 26