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  • meningeal carcinomatosis  (3)
  • 5-FU  (1)
  • 9L glioma  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 45 (1999), S. 9-17 
    ISSN: 1573-7373
    Keywords: ACNU ; MTX ; 5-FU ; pharmacokinetics ; leptomeningeal tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution of radio-labeled ACNU, MTX and 5-FU in brain and tumor tissue was studied in female Wistar rats by macroautoradiography after intrathecal administration. In normal rats, ACNU and 5-FU, administered intracisternally, distributed rapidly in the subarachnoid space, ventricular system and cerebrospinal fluid (CSF). 5-FU and MTX penetrated the brain deeply; the diffusional transport of ACNU was limited to a depth of 1 or 2 mm from the CSF surface of the brain. MTX and 5-FU clearance into the blood circulation was rather slow while ACNU cleared relatively quickly. The half time of ACNU, 5-FU and MTX radioactivity at the ventricular surface was 10, 21, and 110 min, respectively, at their maximal concentration after intracisternal administration. In rats with leptomeningeal tumor induced by intracisternal inoculation of Walker 256 cells, the distribution patterns of ACNU, 5-FU, and MTX were essentially the same as in normal rats despite 10–20 cell layers of tumor growing in the subarachnoid space. 5-FU and MTX were able to penetrate tumor masses in the subarachnoid space; MTX penetration was slower than that of 5-FU and ACNU failed to penetrate to more than a depth of 1 or 2 mm from the tumor surface.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7373
    Keywords: brain tumor ; meningeal carcinomatosis ; cerebrospinal fluid ; biochemical tumor marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary CSF beta-glucuronidase, polyamines and carcinoembryonic antigen (CEA) were analyzed in 16 patients with meningeal carcinomatosis from solid tumor in systemic organs, 27 with benign brain lesions, 18 with primary brain tumors, 14 with metastatic brain tumors and 5 with leptomeningeal dissemination of other malignant diseases. Beta-glucuronidase levels in all cases of meningeal carcinomatosis, meningeal gliomatosis and meningeal lymphoma were higher than 100 μg/dl/hr; on the other hand, levels in all cases of benign brain lesions were below 100 μg/dl/hr. Levels of beta-glucuronidase and polyamines were not high in the cases with positive cytology after tumor resection. Polyamine levels were below 0.05 nmol/ml in all cases after resection of the metastatic brain tumor. Cystic fluid of malignant tumors showed high levels of beta-glucuronidase and polyamines. On the other hand, the levels of polyamines in the cystic fluid of benign tumor were low, although the levels of beta-glucuronidase were high. Some cases of meningeal carcinomatosis with high levels of serum CEA did not show high levels of CSF CEA. For metastatic brain tumors, the cases with intraparenchymal tumors, especially with dural attachment showed high levels of beta-glucuronidase and CEA preoperatively, but they returned to normal after surgery. In cases of meningeal carcinomatosis treated by intrathecal chemotherapy with methotrexate (MTX) and cytosine arabinoside (Ara-C), CSF beta-glucuronidase reflected the neurological status better than the cell count decreased rapidly following chemotherapy and beta-glucuronidase was considered as a useful CSF marker in cases of meningeal carcinomatosis to monitor the course of the disease. The same situation was observed in CSF CEA and CEA was also considered as a useful marker when CEA levels in CSF are higher than those in serum.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7373
    Keywords: meningeal carcinomatosis ; intrathecal chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The records of thirty-four patients with meningeal carcinomatosis treated at our hospital between 1984 and 1990 were reviewed. The sources, histologies, metastatic lesions outside the central nervous system, the history of the treatment of primary lesions and intraparenchymal of metastatic brain tumors and the period from the diagnosis of primary lesions and the treatment of intraparenchymal metastatic brain tumors to the diagnosis of meningeal carcinomatosis were investigated. Meningeal carcinomatosis was diagnosed and by neurological signs, CSF cytology, CT scan and MRI. Each patient was given a 5 mg single dose of methotrexate (MTX) alone or combined with 20 mg cytosine arabinoside (Ara-C) adminstered by intrathecal injection via an Ommaya reservoir and standard lumbar puncture with or without radiotherapy. Following intrathecal chemotherapy 22 of 29 patients showed symptomatic improvement of meningeal irritation and in 10 of 29 patients with cranial nerve impairment amelioration of symptoms was also observed. Moreover, CSF cytology became negative in 10 of 29 patients after a full course of intrathecal chemotherapy. Neurotoxicity Leukoencephalopathy, a neurotoxic effect of intrathecal chemotherapy was not observed in any of the patients. From these results, MTX in small doses is recommended for intrathecal chemotherapy of meningeal carcinomatosis to prevent neurotoxicity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7373
    Keywords: meningeal carcinomatosis ; immunohistochemistry ; glial fibrillary acidic protein ; tubulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of leptomeningeal tumor on the brain parenchyma was studied by the immunohistochemical method with astroprotein (GFAP) and tubulin in a rat model of meningeal carcinomatosis. Thickening of subpial glial lining (external glial layer) and hypertrophy of subpial astrocytes, detected by the antiserum to GFAP, was the early sign of parenchymal involvement. The glial lining was continuous as far as the tumor cells were confined to the subarachnoid space, however, penetration of tumor cells into subpial brain was associated with disruption of the glial lining. Speculative role of this lining in preventing the tumor cell to infiltrate into brain tissue was discussed. In contrast to the prominent immunohistochemical changes in astrocytes, neuronal tubulin immunoreactivity was not altered even in the late stage of the disease. The present study demonstrated that the leptomeningeal dissemination of tumor cells did cause pathologic change in brain parenchyma as was evidenced by the reactive change of astrocytes. However, the preserved immunoreaction for tubulin suggested that the nerve cell damage was not severe even at the advanced stage of the disease.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7373
    Keywords: drug resistance ; ACNU-resistant gliomas ; C6 glioma ; 9L glioma ; reserpine ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to study the mechanism of the resistance to chemotherapeutic agents, especially ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride], two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU were selected in vivo from rat C6 and 9L glioma, respectively. Uptake and efflux of ACNU in these resistant cells were studied with Ethylene[14C]ACNU. The result indicated that the resistance exhibited by both sublines were due to both the reduced uptake of the drug and the increased efflux. The study of the effects of oxidative phosphorylation inhibitor, DNP (2,4-dinitrophenol), on the uptake and retention of ACNU suggested that there is an active outward transport mechanism for ACNU in both glioma sublines and that enhanced activity of this efflux mechanism renders cells highly resistant to the cytotoxic action of ACNU. In an attempt to clarify the more detailed biochemical mechanisms of this active efflux system, we surveyed various membrane-modifying agents which potentiate the sensitivity of these resistant cells to ACNU. Among a number of membrane-modifying agents, reserpine was found to retain ACNU in the resistant cells and to enhance the action of ACNU on these resistant cell lines. It may be concluded that drugs such as reserpine may overcome a mechanism of ACNU resistance.
    Type of Medium: Electronic Resource
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