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)

Advances in chemotherapy have increased the indications for insertion of cerebrospinal fluid (CSF) reservoirs in the treatment of both primary and secondary central nervous system neoplasia. There have been no recent evaluations of the current indications and complications of this procedure in a general neurooncology practice. We undertook a retrospective review of our total experience of 60 patients who were implanted with CSF reservoirs between November 1977 and October 1983. The mean age of those implanted was 38 years (range, 22 months to 79 years). The reasons for insertion were: drug instillation, 35 cases (58.3%); drug level monitoring, 15 cases (25.0%); intermittent tumor cyst drainage, 6 cases (15.0%); and syrinx drainage, 1 case (1.6%). Drug level monitoring was most often done in conjunction with specific experimental chemotherapy protocols. There were no complications after primary insertion, but 9 of 60 reservoirs (15%) required revision for technical failure. Revision was much more likely to occur in the presence of an intracranial mass lesion (7 of 34, or 20.5%). The revision rate in cases of meningeal carcinomatosis was only 7.6% (2 of 26). Patients requiring revision included 5 with glioblastoma, 2 with metastatic tumors, and 2 with meningeal carcinomatosis. Four of the 9 patients requiring revisions developed complications (44%). There were three infections with positive CSF cultures and one subdural hematoma. Infected patients included those with multiple craniotomies, prior cranial irradiation, or some form of chemotherapy. We conclude that primary insertion of a CSF reservoir in a patient with neoplastic involvement of the central nervous system is extremely safe, that technical failure tends to occur in the presence of mass lesions, and that the complication rate of repeated insertion is quite high.
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PMID:Expanded role of the cerebrospinal fluid reservoir in neurooncology: indications, causes of revision, and complications. 405 96

The main objective of this retrospective review of clinical and cerebrospinal fluid (CSF) data from 41 patients with intracranial tumors diagnosed between 1975 and 1989, is to report the role that the finding of neoplastic cells in CSF plays, specially when cerebral CT-scanning and MRI were not currently done. Another objective is to study the CSF proteic abnormalities in cerebral tumors. CSF cell count, cytomorphologic pictures obtained after sedimentation and protein findings are described. Tumor cells were seen in 12 cases (29%): medulloblastomas--6, meningeal carcinomatosis--3, multiforme glioblastoma--1, ependymoma--1, cerebral metastasis--1; in two cases it was an unexpected finding. We noticed that tumoral localization next to the ventricles favoured cell exfoliation. Although pleocytosis was rare and uncorrelated with the presence of neoplastic cells, pathological cytomorphologic pictures appeared in most of the cases including all "positive" ones. Our results stress that the appearance of neoplastic cells in CSF remains helpful specially when it is an unexpected finding.
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PMID:Cerebrospinal fluid cytomorphologic findings in 41 intracranial tumors: a retrospective review. 748 27

To evaluate the possible clinical intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for malignant brain tumors, its anti-tumor activity and neurotoxicity were compared with that of 5-fluorouracil (5-FU) and 5-fluorouridine (FUrd) in vitro. FdUrd showed good tumoricidal activity against cultured mouse 203 glioma cells and rat Walker 256 carcinoma cells as well as A172 human glioblastoma cells. Daoy human medulloblastoma cells and CADO-LC4 human lung cancer cells. It also showed less toxicity for primary cultures of neurons from C57/BL6 mouse and human embryo compared to 5-FU and FUrd. Thymidine phosphorylase (TPase) and thymidine kinase (TK), key enzymes for metabolism of 5-FU derivatives, were measured in cerebrospinal fluid (CSF). TPase or TK activity was detected in the CSF of hardly any patients with malignant brain tumors including meningeal carcinomatosis. These data indicated that the CSF is a favorable site for FdUrd chemotherapy, because the rate of conversion of FdUrd injected to 5-FU would be minimal. In conclusion, FdUrd may be potentially useful for intrathecal treatment of meningeal carcinomatosis.
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PMID:[In vitro study on intrathecal application of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant tumor]. 975 55

Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene were highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect could also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and to prolonged survival. Our study thus demonstrated the efficacy of CD suicide gene therapy for the treatment of peritoneal carcinomatosis.
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PMID:Cytosine deaminase suicide gene therapy for peritoneal carcinomatosis. 1067 52

One of the specific forms of progression of malignant tumors of the central nervous system is meningeal dissemination. Meningeal dissemination is a condition in which tumor cells migrate to the brain surface and sub arachnoid space via cerebrospinal fluid and then infiltrate there. This condition can arise from both primary and metastatic brain tumors, with reported incidences of 4.2% for primary tumors and 5.1% for metastatic tumors. Meningeal dissemination frequently arises from germinoma, medulloblastoma, ependymoma and glioblastoma in cases of primary brain tumors and frequently arises from breast cancer, lung cancer and gastric cancer in cases of metastatic brain tumors, known as meningeal carcinomatosis. The prognosis of meningeal dissemination is poor, and conventional treatments such as systemic chemotherapy and radiation therapy are ineffective. Intrathecal infusion of anti neoplastic agents is one of the options for treatment of meningeal dissemination. The advantage of intrathecal chemotherapy is that the anti neoplastic agent is rapidly diffused in the sub arachnoid space, and its duration of activity is long due to its slow clearance and metabolism. Routes of administration include infusion into the lateral ventricle by puncture of the Ommaya reservoir, infusion into the sub arachnoid space by lumbar puncture, or both of these procedures performed alternately or simultaneously, and methods of infusion include bolus injection and ventriculo lumbar perfusion. Commonly used drugs include methotrexate (MTX), cytarabine (Ara-C), and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)- 1-nitrosourea hydrochloride (ACNU), and some new drugs have also begun to be used clinically. Although there are differences depending on the histological type of the tumor, the anti neoplastic agent administered and the method of administration, the response rate is about 40-80% and mean survival time is about 4-25 months. Although side effects of the anti neoplastic agents are not as severe as with agents used for systemic chemotherapy, specific side effects include nonspecific drug-induced meningitis or ventriculitis, transient or permanent paralysis and leukoencephalopathy. These side effects can be alleviated by reducing the dose or discontinuing the anti neoplastic agents, and a small dose of an adrenocorticosteroid is sometimes administered simultaneously. Bacterial meningitis is another complication and requires discontinuation of anti neoplastic agents, removal of the Ommaya reservoir, or systemic or intrathecal administration of antibiotic agents. Although meningeal dissemination is a rare metastatic condition with a poor prognosis, there have been some reports of successful treatment using this method, which is expected to be widely used in the future.
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PMID:[Intrathecal infusion of the antineoplastic agents for meningeal dissemination]. 1863 17

A 65-year-old woman presented with progressive gait disturbance. She complained of appetite loss for 3 months. Her gait gradually became unsteady, and she was admitted to our hospital. On admission, slow mentation, bathyhypesthesia in left upper and both lower extremites, positive Romberg sign and wide-based gait were observed. Gd-enhanced MRI revealed mass lesions in the left temporal fossa and the cervical spinal canal with focal meningeal enhancement. Besides lesions in the central nervous system (CNS), systematic examination detected no additional malignancy. Repeated cytology of the cerebrospinal fluid was negative. After admission, her consciousness became reduced gradually. At 2 months after admission, she died of central respiratory failure. On autopsy, diffuse extension of the tumor cells was observed on the surface of CNS, and the mass lesions observed by MRI were extra-parenchymal On microscopic examination, the mass was consisted of GFAP positive malignant cells, and included perivascular pseudorosette, pseudopalisading necrosis and many mitotic cells. The diagnosis of the case was made as primary diffuse leptomeningeal gliomatosis (PDLG). PDLG is a rare disorder that is difficult to diagnose by CSF cytology. The progress of PDLG is rapid, and appropriate treatment is rarely taken. However, the combination of temozolomide and the radiotherapy performed for a glioblastoma has been reported as a possible treatment for PDLG. We emphasize that, in possible cases of PDLG, a biopsy should be performed in the early stages, especially in cases showing features similar to those of metastatic meningeal carcinomatosis and have no malignant tumors by whole body examination.
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PMID:[A case of primary diffuse leptomeningeal gliomatosis, clinically indistinguishable from metastatic meningeal carcinomatosis]. 2148 65

Extraneural metastatic disease resulting from a primary central nervous system neoplasm is a rare clinical finding in the pediatric population. We report a case of peritoneal glioblastoma carcinomatosis following placement of a ventriculoperitoneal shunt and chemoradiotherapy in a 6-year-old female patient who initially presented with diffuse intrinsic pontine glioma. This case demonstrates the importance of evaluation of extraspinal structures when imaging for extension of disease. Additionally, this report highlights the cross-sectional imaging characteristics of glioblastoma peritoneal carcinomatosis and presents additional information that will facilitate the timely diagnosis of extraneural metastases of primary high-grade glial neoplasms in the pediatric population.
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PMID:Metastatic Diffuse Intrinsic Pontine Glioma to the Peritoneal Cavity Via Ventriculoperitoneal Shunt: Case Report and Literature Review. 2625 21

Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery. We reviewed completed clinical trials for the treatment of glioblastoma and metastatic colorectal cancer and examined the data in these studies for safety, efficacy, and potential advantages that regional delivery may confer over systemic delivery. Our appraisal of the available literature revealed that regional delivery of CAR-T cells in both glioblastoma and hepatic colorectal metastases was generally well tolerated and efficacious in select instances. We propose that the regional delivery of CAR-T cells is an area of potential growth in the solid tumor immunotherapy, and look towards future clinical trials in head and neck cancer, mesothelioma, and peritoneal carcinomatosis as the use of this technique expands.
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PMID:Regional Delivery of Chimeric Antigen Receptor (CAR) T-Cells for Cancer Therapy. 2871 15

Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic cancer that disproportionately affects patients with advanced breast cancer. Moreover, those with BRCA1/2-mutated disease more often experience leptomeningeal metastasis. Treatment options for LC are limited and often include significant toxicities. PARP inhibitors offer an important potential treatment for patients with BRCA1/2-mutated breast and ovarian cancers, but clinical studies excluded patients with central nervous system (CNS) metastases, including LC. Efficacy data in this area are therefore limited, although a phase I study of olaparib in glioblastoma did show CNS penetration. Here we report a case of a patient with BRCA2-mutated breast cancer and solitary recurrence in the leptomeninges with ongoing complete response to treatment with the PARP inhibitor olaparib. PARP inhibitors may be an important treatment option for patients with BRCA-mutated disease and LC, and warrant further study.
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PMID:Response to Olaparib in a Patient with Germline BRCA2 Mutation and Breast Cancer Leptomeningeal Carcinomatosis. 3181 82