Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.
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PMID:Permanent I-125 brain stem implants in children. 984 Mar 81

Central nervous system (CNS) tumors are the most common solid neoplasms in children. Medulloblastomas (MEDs) resemble embryonic neuroectodermal stem cells and their immature, uncommitted neuronal and glial progeny. Apoptosis is a basic physiological process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and finally, disintegration of the cell into small, membrane-bound apoptotic bodies. Expression of Fas (APO-1, CD95) receptor (FasR) and programmed or active cell death (PCD) was studied in childhood MEDs with varying stages of malignancy, and cell differentiation features. The majority of neoplastically transformed, neuroectodermal in origin cells, particularly in MEDs, express FasR, whereas normal cells in the CNS do not. FasR is a transmembrane glycoprotein, which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within childhood PNETs/MEDs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with anti-section i FasR antibodies. The resence of FasL has also been detected in childhood glial tumors. Therefore, a spontaneous, cellular immunophenotype (IP) regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood brain tumors during neoplastic growth and progression. During our systematic immunocytochemical screening, we employed formalin fixed, paraffin-wax embedded tissue sections, as well as frozen sections of 34 primary human childhood PNETs/MEDs. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique, modified by us, provided excellent immunocyto-chemical results. A systematic observation of the presence of apoptosis related markers (especially FasR) and cells in PCD was carried out. A strong expression (intensity of staining: "A"-the highest possible; number of stained neoplastic cells: +3 to +4, between 50% to 90%) of FasR, was detected employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colon epithelium. Certainly, the coexpression of FasR, FasL, and other PCD-related proteins have also been reported in other human malignancies: breast cancer, colorectal carcinomas, large granular lymphocytic leukemia of T or NK cell origin, melanomas, lung, prostate, pancreas, and hepatocellular carcinomas. The coexpression of both FasR and FasL on several neoplastic cell types may represent an effective mechanism for tumor escape of the cellular immunological response of the host. It has been well established that brain tumors and melanomas produce their autocrine FasL, and even become capable of switching their signal transduction from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) represents a new and exciting immunotherapeutical possibility in the treatment of primary childhood neuroectodermal tumors.
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PMID:Fas (APO-1, CD95) receptor expression and new options for immunotherapy in childhood medulloblastomas. 1065 26

Galectin-3 is a member of the galectin family of beta-galactoside-specific animal lectins. Here we show that galectin-3 is constitutively expressed in 15 out of 16 glioma cell lines tested, but not by normal or reactive astrocytes, oligodendrocytes, glial O-2A progenitor cells and the oligodendrocyte precursor cell line Oli-neu. Galectin-3 is also expressed by one oligodendroglioma cell line, but not by primitive neuroectodermal tumor and 4 neuroblastoma cell lines tested so far. In all galectin-3 expressing cell lines, the lectin is predominantly, if not exclusively, localized intracellularly and carries an active carbohydrate recognition domain (shown for C6 rat glioma cells). Moreover, in contrast to primary astrocytes, glioma cells do not or only weakly adhere to substratum-bound galectin-3, probably reflecting an unusual glycosylation pattern. Our findings indicate that the expression of galectin-3 selectively correlates with glial cell transformation in the central nervous system and could thus serve as a marker for glial tumor cell lines and glial tumors.
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PMID:Expression pattern of galectin-3 in neural tumor cell lines. 1072 67

The surgical pathology of intramedullary spinal cord neoplasms is most accurately based on radical resection specimens rather than on small biopsies, which may be highly misleading. A review of the neuropathology files at NYU Medical Center revealed 294 surgical specimens of intramedullary cord lesions examined between January 1, 1991 and December 31, 1998. Of these 117 were from children (age less than 21 years) and 177 were from adults (21 and over). While most types of central nervous system tumors known to occur in the brain also occur in the spinal cord, the different proportions of these tumors by histologic type, and the differences in the proportions of tumor types in children compared to adults, are both significant. In adults ependymomas are the predominant tumor type (93 total) while in children astrocytomas and mixed neuronal-glial tumors are virtually equally common and outnumber ependymomas. In this period no cord Primitive Neuroectodermal Tumors were identified. Among the astrocytic neoplasms and other gliomas, high grade tumors were distinctly uncommon in children and only slightly more common in adults, in sharp contrast with the brain, where the majority of adult intra-axial tumors are high grade.
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PMID:Surgical pathology of intramedullary spinal cord neoplasms. 1101 35

Mammalian cells are capable of committing "active suicide" or apoptosis in response to specialized pathological mechanisms employing a phylogenetically developed intrinsic program of death, triggered by signal transduction through specific receptors. Changes in cellular structure such as: 1) condensation of the nuclear (chromatin) and cytoplasmic structures (especially the mitochondria); 2) blebbing of the cell membrane; 3) characteristic swelling of the endoplasmic reticulum; and 4) fragmentation of the cells in membrane bound apoptotic bodies, are the dramatic signs of total cell destruction. Apoptosis requires energy in the from of ATP, indicating that programmed cell death (PCD), as opposed to necrosis, is an energy dependent, active physiological and pathophysiological phenomenon. During this immunocytochemical study, we observed the presence of PCD in the prenatal thymus and various human neoplastically transformed tissues. During the intrauterine ontogenesis, in thymocytes or resting T lymphocytes, p53 tumor suppressor protein was identified to be a critical mediator of PCD in response to DNA damage. The cellular interaction of immature, cortical thymocytes (characterized by a double positive CD4+CD8+TCRlow immunophenotype-IP) with thymic RE cells induces positive selection of T lymphocytes that recognize, but are not activated, by self-MHC molecules (tolerance induction). Double positive CD4+CD8+CD3- thymocytes undergo FasL-mediated apoptosis, while CD4+CD8+CD3+ cells use the CD3 mediated pathway of PCD. Two step, apoptotic cell death is mainly restricted to the CD4+CD8+TCR dull thymocyte subpopulation. T-lymphocytes which do not undergo positive selection are killed by apoptosis in response to a number of intrinsic and extrinsic factors, such as chemical toxins, viral infections, X- and UV irradiation, mild hyperthermia, the actions of various hormones, extracellular survival factors, calcium ionophores (such as A23187), various chemotherapeutic drugs (adriamycin, actinomycin D, etc) and antibodies directed to the CD3-TCR (T cell receptor) complex. Immature thymocytes also undergo a second selective process, so-called negative selection, when thymic stromal cells eliminate autoreactive T lymphocytes. As a typical model of embryonal neoplasms, we observed 34 childhood PNET/MED tissues samples. A systematic observation for the presence of apoptosis related markers (especially FasR) and cells in PCD was carried out. A strong expression (intensity of staining: "A"--the highest possible; number of stained neoplastic cells: +++ to ++++, between 50% to 90%) of FasR was detected. We also observed 42 childhood glial tumors, divided as follows: 6 pilocytic ASTRs; 14 low grade ASTRs; 16 anaplastic ASTRs; and 6 GBMs. The GBMs represent an end-stage brain tumor IP dedifferentiation of glial origin. During the immunocytochemical screening of these 42 childhood ASTRs, we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: ++ to ++++, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR expression was rated high, 70% to 90% on the tumor cells in pylocytic ASTRs, lowered to 50% to 60% on the neoplastic cells in low grade ASTRs, even lower between 30% to 40% in anaplastic ASTRs and significantly lower, between 20% to 35% on the neoplastically transformed cells of GBM tissues. The presence of apoptotic neoplastic cells was also regularly detected in other human adult neoplasms, such as thyroid, pancreatic, hepatocellular, gastric, colon, breast, ovarian, prostata, and renal cell carcinomas, as well as, in Hodgkin and non-Hodgkin lymphomas and some sarcomas. The expression of apoptosis related cell surface molecules on the surface of both neoplastically transformed cells and on tumor cell specific, cytotoxic T lymphocyte (CTL) surfaces (FasR-FasL system) raises a distinct possibility of active PCD induction in CTL by tumor cells. Juxtacrine interactions between CTL and neoplastically transformed cells, coupled with observations that tumor cells can modulate the intracellular, signaling domains of cell surface receptors to elicit responses quite often contrary to the expected, may even provide a way for CTL to enhance the proliferation and dedifferentiation of cancer cells. Adoptive cellular immunotherapies employing CTL raised against autologous neoplastically transformed cells in vitro should be employed in the control of minimal residual disease following surgical resection of the primary malignant growth.
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PMID:The role of apoptosis in normal ontogenesis and solid human neoplasms. 1120 98

We examined the cytotoxicity of the immunosuppressant agent rapamycin and its analogue CCI-779 in human brain tumor cell lines in vitro and in vivo as single agents and in combination with standard chemotherapeutic drugs. In the rapamycin-sensitive PNET/MB cell line DAOY, rapamycin exhibited additive cytotoxicity with cisplatin and with camptothecin. In vivo, CCI-779 delayed DAOY xenograft growth by 160% after 1 week and 240% after 2 weeks of systemic treatment, compared with controls. Single high-dose treatment induced 37% regression of tumor solume. Growth inhibition of DAOY xenografts was 1.3 times greater after simultaneous treatment with CCI-779 and cisplatin than after cisplatin alone. Interestingly, CCI-779 also produced growth inhibition of xenografts derived from U251 malignant glioma cells, a human cell line resistant to rapamycin in vitro. These studies suggest that the rapamycin analogue CCI-779 is an important new agent to investigate in the treatment of human brain tumors, particularly PNET/MB.
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PMID:Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy. 1124 61

DNA damage produces delayed mitosis (G2/M delay) in proliferating cells, and shortening the delay sensitizes human malignant glioma and medulloblastoma cells to cytotoxic chemotherapy. Although activation of the cyclin-dependent kinase CDC2 mediates G2/M transition in all tumor cells studied to date, regulation of CDC2 varies between tumor types. Persistent hyperphosphorylation of kinase and reduced cyclin expression have been implicated as mediators of treatment-induced G2 delay in different tumor models. To evaluate regulation of G2/M transition in human brain tumors, we studied the expression and/or activity of CDC2 kinase and cyclins A and B1 in U-251 MG and DAOY medulloblastoma cells after their treatment with camptothecin (CPT). Synchronized cells were treated during S phase, then harvested at predetermined intervals for evaluation of cell cycle kinetics, kinase activity mRNA, and protein expression. CPT produced G2 delay associated with decreased CDC2 kinase activity and cyclin B1 expression. Kinase activity was associated with CDC2 bound to cyclin B1, not cyclin A, in both cell lines. Cyclin A mRNA and protein expression were reduced after CPT treatment; however, decreased protein expression was short lived and moderate in the glioma and primitive neuroectodermal tumor/medulloblastoma cells, respectively. We conclude that G2 delay is a common response of brain tumor cells to chemotherapy with topoisomerase I inhibitors and that a mechanism of this delay may be reduced expression of cyclin B1.
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PMID:Decreased cyclin B1 expression contributes to G2 delay in human brain tumor cells after treatment with camptothecin. 1130 12

The present case involved a 70-year-old woman who was diagnosed with a right cerebral hemorrhage. Excisional surgery of the hematoma was performed. Grossly, a whitish, solid tumor (1 x 1 x 0.8 cm in size) was recognized in the hematoma. Histologically, the tumor was composed of large, polygonal cells and small undifferentiated cells in a jumbled architectural arrangement with a cartilage component. The large, polygonal cell component was conspicuous and somewhat rhabdoid in appearance and appeared to be an astrocytic tumor showing glial differentiation. The small, undifferentiated cell component resembled tumor cells of a primitive neuroectodermal tumor (PNET). Clinical follow-up of the patient for 2 months after the first operation revealed recurrence with rapid growth. A second operation was performed, but the patient died 8 months after the first operation (2 months after the second). Immunohistochemically, the tumor cells suggesting glial differentiation were positive for glial fibrillary acidic protein (GFAP), S-100, neuron-specific enolase (NSE), and vimentin. PNET-like components in the primary tumor were positive for NSE, GFAP, and S-100, and weakly positive for vimentin and synaptophysin. Each tumor cell was negative for epithelial membrane antigen (EMA), keratin, desmin, actin, myoglobin, neurofilament (NF), and MIC2 protein. The recurrent tumor revealed predominantly PNET-like components; however, only a few tumor cells were positive for GFAP. This appearance suggested that this brain tumor might originate from a common multipotential stem cell. Considering its histopathological and immunohistochemical characteristics, the primary tumor was finally regarded as an undifferentiated glioma with dedifferentiation of the glial component in the recurrent tumor.
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PMID:A case of undifferentiated glioma in a 70-year-old woman. 1151 75

Rhabdoid phenotypic change has been described in a number of different neoplasms from diverse organ sites. These tumors share common light and electron-microscopic features, display a polyphenotypic immunohistochemical profile and often show cytogenetic abnormalities of chromosome 22. In the central nervous system (CNS), most rhabdoid tumors occur in the posterior fossa of very young children and are associated with a primitive neuroectodermal tumor (PNET) component and are designated atypical teratoid/rhabdoid tumors. Infrequently, other rhabdoid tumors of the CNS have been described, including rhabdoid meningiomas and malignant rhabdoid tumors of uncertain histogenesis. Several examples of conventional gliomas displaying significant areas with rhabdoid morphology were also presented in an abstract by Kepes and Moral [1991], although never published in final manuscript form. We now detail the case of an 18-year-old male with an aggressive, supratentorial CNS rhabdoid tumor that was associated with an epithelioid glioblastoma and apparently arose from areas of low-grade glioma. The rhabdoid tumor component was present in the original tumor but became more predominant with each of 3 successive resections. No areas of PNET were identified. Electron microscopy and immunohistochemistry showed features classic for rhabdoid tumors and cytogenetic studies demonstrated multiple tumor clones with monosomy 22. This case documents progressive rhabdoid transformation of a glioma, expands the spectrum of CNS tumor types that can display a rhabdoid phenotype and highlights the diagnostic and therapeutic challenges with this type of tumor.
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PMID:Rhabdoid glioblastoma. 1175 80

A phase II study of irinotecan (CPT-11) was conducted at Duke University Medical Center, Durham, NC, to evaluate the activity of this agent in children with high-risk malignant brain tumors. A total of 22 children were enrolled in this study, including 13 with histologically verified recurrent malignant brain tumors (glioblastoma multiforme [GBM] 4, anaplastic astrocytoma 1, ependymoma 5, and medulloblastoma/primitive neuroectodermal tumor 3), 5 with recurrent diffuse pontine glioma, and 4 with newly diagnosed GBM. All patients with recurrent tumor had prior chemotherapy and/or irradiation. Each course of CPT-11 consisted of 125 mg/m ( 2 ) per week given i.v. for 4 weeks followed by a 2-week rest period. Patients with recurrent tumors received therapy until disease progression or unacceptable toxicity. Patients with newly diagnosed tumors initially received 3 cycles of treatment to assess tumor response and then were allowed radiotherapy at physician's choice; patients who demonstrated a response to CPT-11 prior to radiotherapy were allowed to continue the drug after radiation until disease progression or unacceptable toxicity. A 25% to 50% dose reduction was made for grade III-IV toxicity. Responses were assessed after every course by gadolinium-enhanced MRI of the brain and spine. Twenty-two patients received a median of 2 courses of CPT-11 (range, 1-16). Responses were seen in 4 of 9 patients with GBM or anaplastic astrocytoma (44%; 95% confidence interval, 11%-82%) (complete response in 2 patients with recurrent GBM lasting 9 months and 48+ months; partial response in one patient with a newly diagnosed midbrain GBM lasting 18 months prior to radiotherapy; and partial response lasting 11 months in 1 patient with recurrent anaplastic astrocytoma), 1 of 5 patients with recurrent ependymoma (partial response initially followed by stable disease lasting 11 months), and none of 5 patients with recurrent diffuse pontine glioma. Two of 3 patients with medulloblastoma/primitive neuroectodermal tumor had stable disease for 9 and 13 months. Toxicity was mainly myelosuppression, with 12 of 22 patients (50%) suffering grade II-IV neutropenia. Seven patients required dose reduction secondary to neutropenia. CPT-11, given in this schedule, appears to be active in children with malignant glioma, medulloblastoma, and ependymoma with acceptable toxicity. Ongoing studies will demonstrate if activity of CPT-11 can be enhanced when combined with alkylating agents, including carmustine and temozolomide.
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PMID:Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience. 1191 1


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