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)

Various histological types of tumors arise in the pineal region. The most common tumors are pineal parenchymal tumors and germ cell tumors. Pineal parenchymal tumors are divided into pineocytoma, pineal parenchymal tumor with intermediate differentiation and pineoblastoma. Pineocytomas are well-differentiated tumors and retain the morphological and immunohistochemical features of pineal parenchymal cells. Lobular architectures and pineocytomatous rosettes are also typical features. In contrast, pineoblastomas are embryonal tumors resembling primitive neuroectodermal tumors (PNET). However, pineoblastomas are distinct from PNET in other sites due to their exhibiting photosensory differentiation including Flexner-Wintersteiner rosettes and fleurettes. Although pineal cysts are tumor-like lesions, and not true neoplasms, they are occasionally difficult to distinguish from pineocytoma and astrocytoma. From the therapeutic aspect, a precise differential diagnosis is critical. The pineal region is the most common site of the brain in which germ cell tumors occur. Germinoma, teratoma, embryonal carcinoma, yolk sac tumor and choriocarcinoma are encountered, and the latter three types of tumors usually constitute elements of mixed germ cell tumors. The morphological and immunohistochemical features of intracranial germ cell tumors are very similar to those of gonadal germ cell tumors, although there are some differences in germinoma. Pineal germinoma may exhibit carcinomatous differentiation. Other types of tumors are occasionally observed, including fibrillary and pilocytic astrocytoma, glioblastoma, ependymoma, melanoma, meningioma and so on. Metastatic pineal tumors are also rare. The most common site of origin for pineal metastasis is the lung.
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PMID:Pathology of pineal region tumors. 1176 90

The existence of tumorspheres (TSs) might confer treatment resistance to pineoblastoma (PB). The existence of PB TSs with cellular immortalization potential has not yet been reported. We developed a procedure for isolating TSs from recurrent PB (rPB) and tested whether their properties made them suitable for use as a patient-derived xenograft (PDX). Immunocytochemical staining, RT-PCR and quantitative real-time PCR showed that, among stemness proteins, CD133, musashi and podoplanin were expressed at elevated levels in rPB TSs, but nestin was not. rPB TSs cultured under neuro-glial differentiation conditions expressed TUBB3, but not GFAP, MBP or NeuN. Unlike glioblastoma TSs, rPB TSs showed no clear evidence of invasion in 3D invasion assay or increased expression of genes associated with epithelial-mesenchymal transition. An orthotopic xenograft showed that tumor xenografts replicated the histopathological features of the patient tumor and expressed similar genome profiles, as determined by short tandem repeat genotyping. These data demonstrate the isolation and the characterization of rPB TSs for the first time. Using an orthotopic xenograft, we showed that rPB TSs could replicate the patient tumor, demonstrating their potential as a PDX for precision medicine.
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PMID:Isolation and characterization of tumorspheres from a recurrent pineoblastoma patient: Feasibility of a patient-derived xenograft. 2727 49

Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with significant long-term debilitating side effects. The prognosis for pineoblastoma is age-dependent, with little chance of a cure for children younger than three years. More effective molecularly targeted strategies are urgently required to treat these cancers. Hyper-activation of epidermal growth factor receptor (EGFR) signaling is characteristic of several different classes of human cancers, including a subset of glioblastoma and medulloblastoma. This has provided the impetus for the development of a suite of EGFR pathway blockers, including second generation irreversible inhibitors, such as dacomitinib. We have developed a comprehensive drug evaluation pipeline, including in vitro interaction analyses and orthotopic xenograft mouse models, to address the efficacy of drugs for brain tumor treatment, enabling the exclusion of potentially ineffective treatments and prioritization of truly beneficial novel treatments for clinical trial. We used this system to examine the effects of dacomitinib as a single agent, or in combination with conventional chemotherapeutics, on the growth of human adult and pediatric brain tumor cell lines. Dacomitinib inhibited EGFR or EGFRvIII activity in vitro in all three tumor types tested, and as a single agent induced a modest increase in survival time for mice bearing glioblastoma, which accurately predicted human clinical trial data. For pediatric medulloblastoma, dacomitinib blocked EGFR/HER signalling in orthotopic xenografts and extended median survival as a single agent, however was antagonistic when used in combination with standard frontline medulloblastoma chemotherapies. The findings caution against the use of dacomitinib for pediatric brain tumor clinical trials.
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PMID:A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors. 2957 50

As genomic characterization becomes increasingly necessary for accurate diagnosis of tumors of the central nervous system, identification of rapidly assessible biomarkers is equally important to avoid excessive cost and delay in initiation of therapy. This article reviews novel immunohistochemical markers that may be used to determine mutation status, activation of signaling pathways, druggable targets, and cell lineage in many diverse tumor types. In particular, recently added entities to the 2016 WHO classification of central nervous system tumors will be addressed, including IDH-mutant gliomas, diffuse midline glioma, epithelioid glioblastoma, angiocentric glioma, RELA-rearranged ependymoma, embryonal tumors (medulloblastoma, atypical teratoid/rhabdoid tumor, pineoblastoma, embryonal tumor with multilayered rosettes, and other genetically defined high-grade neuroepithelial tumors), and meningiomas associated with germline alterations.
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PMID:Advances in Diagnostic Immunohistochemistry for Primary Tumors of the Central Nervous System. 3072 Apr 70


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