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)

A multicenter phase I/II trial of a human recombinant interferon beta (Betaseron; Triton Biosciences, Alameda, CA) was conducted in patients with recurrent glioblastoma and anaplastic astrocytoma in six centers between 1986 and 1988. Betaseron was given intravenously three times per week, starting at 90 x 10(6) IU per dose and escalating by 90 x 10(6) IU every 2 weeks up to a maximum dose of 540 x 10(6) per treatment. All patients had failed prior radiotherapy, and most had failed one or more courses of chemotherapy. Of the 72 patients entered into the protocol, 65 were considered assessable. Of 65 patients, 41 had glioblastoma, and 24 had anaplastic astrocytoma. Of the 65 assessable patients, 15 (23%) had an objective response (R), and 18 (28%) had stable disease (S), with a combined R and S rate of 51%. The Kaplan-Meier median time to progression was 24 weeks for the responders, 10 weeks for the nonresponders, and 23 weeks for the whole group. These results suggest that Betaseron has definite activity in recurrent gliomas, with an R + S rate of 51%. The maximum-tolerated dose (MTD) is between 180 and 360 x 10(6) IU, with neurotoxicity being the most troublesome toxicity at higher doses. Two patients died of treatment-related complication. Since most responders showed responses at the 180 x 10(6 IU dose range, further studies using a lower dose of Betaseron aimed at decreasing toxicity and allowing chronic maintenance therapy are merited.
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PMID:Intravenous recombinant interferon beta in patients with recurrent malignant gliomas: a phase I/II study. 154 30

B cell stimulatory factor 2 receptors (BSF-2-R) were studied using radioiodinated recombinant BSF-2 with a specific activity of 6.16 X 10(13) cpm/g. Kinetic studies showed that binding of 125I-BSF-2 to CESS cells reached maximum level within 150 min at 0 degrees C. There was a single class of receptors with high affinity (Kd 3.4 X 10(-10) M) on CESS, and the number of receptors was 2,700 per cell. Binding of 125I-BSF-2 to CESS was competitively inhibited by unlabeled BSF-2 but not by IL-1, IL-2, IFN-beta, IFN-gamma, and G-CSF, indicating the presence of the receptors specific for BSF-2. EBV-transformed B lymphoblastoid cell lines (CESS, SKW6-CL4, LCL13, and LCL14) expressed BSF-2-R, whereas Burkitt's lines did not. EBV or EBNA2 did not induce the expression of the receptors on Burkitt's cells. The plasma cell lines (ARH-77 and U266) expressed BSF-2-R, fitting the function of BSF-2 as plasma cell growth factor. Several other cell lines, the histiocytic line U937, the promyelocytic line HL60, the astrocytoma line U373 and the glioblastoma line SK-MG-4, in which BSF-2 was inducible with IL-1 or TPA, displayed BSF-2-R with Kd in the range of 1.3-6.4 X 10(-10) M, suggesting the autocrine mechanism in BSF-2 function. The four T cell lines (CEM, HSB, Jurkat, and OM 1) did not express a detectable number of receptors, but normal resting T cells expressed 100-1,000 receptors per cell. BSF-2-R were not present on normal resting B cells but expressed on activated B cells with a Kd of 3.6-5.0 X 10(-10) M, fitting the function of BSF-2, which acts on B cells at the final maturation stage to induce immunoglobulin production.
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PMID:Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression. 282 Nov 54

In the present study we have evaluated the effect of recombinant human fibroblast, IFN-beta ser, and immune, IFN-gamma, interferon, alone and in combination, on the proliferation of fifteen early passage human glioblastoma cell cultures. Explant cultures were established from glioblastoma tumor tissue obtained at the time of surgery. After sufficient outgrowth, cultures were dispersed with trypsin/versene and maintained as independent cell lines. IFN-beta ser induced a greater than or equal to 50% reduction in the 7 day growth of 6 of the 15 cultures. The majority of cultures, 9 of 15, displayed less than or equal to 50% growth suppression in comparison with control cultures after 7 days exposure to 2000 Units/ml of IFN-beta ser. When treated with 2000 Units/ml of IFN-gamma, only 1 of the 15 glioblastoma cultures exhibited a greater than or equal to 50% reduction in growth. In contrast, when treated with the combination of IFN-beta ser plus IFN-gamma, 1000 Units/ml of each interferon preparation, 12 of 15 cultures were inhibited by greater than or equal to 50% after 7 days growth. The combination of interferons was effective in suppressing glioblastoma growth both in cultures displaying relative sensitivity and those exhibiting innate resistance to either or both types of interferon when employed alone. One glioblastoma culture, G-7, was studied through 45 passages and displayed the same sensitivity at different passages to growth inhibition when exposed to IFN-beta ser, IFN-gamma or both interferons. Based on previous clinical studies indicating that IFN-beta or IFN-gamma when administered alone to patients do not generally alter the clinical progression of malignant gliomas, the present results suggest that the combination of IFN-beta plus IFN-gamma may prove more effective than either agent alone in the clinical treatment of patients with glioblastoma multiforme.
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PMID:Enhanced in vitro growth suppression of human glioblastoma cultures treated with the combination of recombinant fibroblast and immune interferons. 283 97

In order to analyze the efficacy of combination therapy with Hu-IFN-beta, ACNU and radiation (IAR), nine patients with malignant glioma were treated as a control study. They received 100 X 10(4) IU Hu-IFN-beta daily for seven days intravenously or intratumorally, 3 mg/kg ACNU on day 2 and 5,000-6,000 rads of radiation from day 3. Four out of nine patients showed complete response and one partial response with this IAR therapy. Case 1 was a 64-year-old man who had glioblastoma in the left frontal lobe. Postoperative residual tumors disappeared completely with this therapy. Case 3 was a 8-year-old girl who had an enhanced high-density lesion in the medulla oblongata and pons. After IAR therapy, the high-density lesion was completely vanished and her clinical manifestations of multiple cranial nerve palsy and pyramidal sign were improved remarkably. The major side effects of IAR therapy were mild or moderate myelosuppression, and some patients also showed hepatic dysfunction, mild fever and gastrointestinal toxicities. However, all these side effects were mild and transient and soon recovered to normal levels. These results suggest that IAR therapy is effective and will prolong the survival time of patients with malignant glioma.
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PMID:[Combination therapy with IFN-beta, ACNU and radiation (IAR) in malignant brain tumors]. 345 40

The effects of human interferon-beta (IFN-beta, MR-21) on the growth of xenografted human tumors in nude mice were examined. IFN-beta was administered to mice with malignant melanoma (SK-MEL-28 and Sk-14) intratumorally at a dose of 1 X 10(5)-3 X 10(5) IU/mouse, with acute leukemia (CCRF-HSB-2) intratumorally at a dose of 3 X 10(5) IU/mouse, with glioblastoma (U-373 MG) intravenously or intratumorally at a dose of 1 X 10(5)-6 X 10(5) IU/mouse, or with uterine cervical tumor (HeLa S3) intravenously at a dose of 0.3 X 10(5)-1 X 10(5) IU/mouse. IFN-beta inhibited the growth of all of these tumors in a dose-dependent manner.
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PMID:[Basic study on interferon-beta: Part IV. Antitumor effect on nude mouse-transplanted human tumors]. 371 59

Three types of interferon preparation (alpha, beta and gamma) have been used in the treatment of tumours in vivo. At the time of writing no information is available on IFN-gamma treatment of tumour patients. Treatments with IFN-alpha and IFN-beta have been undertaken at many clinical centres. Both types of preparation can exert side effects. Both types have also been able to cause regression of certain tumours in individual patients. At our hospital, IFN-alpha has been given to tumour patients over the last decade. Antitumour effects have been registered on patients with juvenile laryngeal papillomatosis, Hodgkin's disease, myelomatosis, ovarian carcinoma, hypernephroma and glioblastoma. Further study is needed on how therapy with IFN should best be undertaken and also how such treatment compares with other treatments of various tumour diseases. IFN therapy should also be combined with other such treatments.
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PMID:Interferon therapy in neoplastic diseases. 618 85

Since 1980, phase 1 and 2 clinical trials of Hu-IFN-beta have been done in the field of neurosurgery. In the present study, (1) the results of in vivo experiments of Hu-IFN-beta are reported and (2) the effectiveness of Hu-IFN-beta in patients with malignant brain tumors is also evaluated. (1) The antitumor activities of beta-IFN and poly ICLC in nude mice receiving subcutaneous transplants of human brain tumors (2 strains) were compared with those of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, beta-IFN and poly ICLC, tumor reduction rates were evaluated by the method of Battelle. The effectiveness of beta-IFN and poly ICLC was slightly inferior to that of ACNU and vincristine, although tumor reduction rates (treated/control values) of 43% and 39% were respectively obtained with beta-IFN and poly ICLC against one strain of glioblastoma. (2) Clinically, 7 patients with malignant brain tumors were given beta-IFN (4 by intratumor administration and 3 by intravenous injection) in a dose of 3 X 10(6) to 9 X 10(6) IU/day for 2 to 6 months to study the efficiency and side effects of IFN treatment. One of four patients given IFN intratumorally showed a reduction in tumor size (partial response) by CT scan; the three patients injected IFN intravenously were unchanged. There were no noteworthy side effects in the cases treated intratumorally except for fever occurring in one patient. In the patients treated intravenously, however, fever, general malaise, leukopenia and thrombocytopenia were noted.
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PMID:[Effect of human fibroblast interferon on malignant brain tumors]. 665 89

Within the Special Research Group of Department of Health and Welfare, seven research subgroups which are testing different types of interferon supplied from each seven companies are organized at the time of October 1982. Out of these subgroups, two groups, Toray company group (IFN-beta) and Sumitomo company group (HLBI-alpha), have made clinical trials on 123 cases and 120 cases respectively. Other groups are still under preparation. 6 cases with complete response and 23 cases with partial response by IFN-beta, and 0 cases with complete response and 13 cases with partial response by HLBI-alpha are observed. Over all responded disease are such as glioblastoma, medulloblastoma, melanoma and cutaneous T-cell lymphoma with local injection, and hypernephroma, bladder carcinoma, medulloblastoma, multiple myeloma, and adult T-cell leucaemia with systemic administration.
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PMID:[Current status and problems of cancer treatment with interferon]. 687 30

Antineoplaston (Ap), a new antitumor agent, was clinically tested for effects on malignant brain tumors. The materials were 3 cases of glioblastoma (G,B), 2 cases of anaplastic astrocytoma, 1 case of pontine glioma, 2 cases of metastatic brain tumor and 1 case of medulloblastoma. All patients underwent radiochemotherapy and surgical resection of the tumors except the cases of pontine glioma, metastatic brain tumor and anaplastic astrocytoma. For gliomas, radiochemotherapy was used with Hu-IFN-beta. Ap was administered at a dose of 7-10 g/day in combination with remission maintenance therapy of gliomas. Complete response was obtained in one anaplastic astrocytoma. Partial response was obtained in 2 cases, a pontine glioma and a metastatic brain tumor. No change was observed in 2 cases, an anaplastic astrocytoma and a multiple brain metastasis. Progression of the disease was observed in 4 cases, 3 glioblastomas and 1 medulloblastoma, which showed continuous increase in tumor size. The effects of Ap on malignant brain tumors were considered due to synergy, since it was administered with other drugs and acceleration of tumor cellular differentiation. Ap is useful as an approach to remission maintenance therapy for brain tumors.
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PMID:The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. 747 50

To elucidate which cytokine receptors may be expressed by human glioblastoma and normal astrocytic cells, the presence of messenger ribonucleic acid (RNA) for a number of cytokine receptors was examined in 16 glioblastoma cell lines and adult and fetal astrocytes. A complementary deoxyribonucleic acid copy of total RNA was synthesized and amplified with specific primers using the polymerase chain reaction method. The receptors studied were interleukin (IL)-1 receptor type I (IL-1RI) and type II (IL-1RII), p75 and p55 tumor necrosis factor (TNF) receptors (p75TNFR and p55TNFR), interferon (IFN)-alpha/beta and -gamma receptors (IFN-alpha/beta R and IFN-gamma R), granulocyte-macrophage (GM) colony-stimulating factors receptor alpha subunit (GM-CSFR), G-CSF receptor (G-CSFR), M-CSF receptor (c-fms, M-CSFR), stem cell factor receptor (c-kit, SCFR), IL-6 receptor (IL-6R), and IL-8 receptor (IL-8R). Transcripts for IL-1RI, p55TNFR, IFN-alpha/beta R, and IFN-gamma R were present in all cell lines. The presence of IL-1RII, p75TNFR, GM-CSFR, M-CSFR, SCFR, IL-6R, and IL-8R was identified in 13, eight, seven, eight, 14, three, and one cell lines, respectively. Normal astrocytes were positive for IL-1RI, p75TNFR, p55TNFR, IFN-alpha/beta R, IFN-gamma R, M-CSFR, and SCFR, showing a similarity to glioblastoma cells. Expression of IL-1RII was observed in adult astrocytes but not in fetal astrocytes. Furthermore, gene expression was assessed in normal brain tissue and 11 glioblastoma tissue specimens. The normal brain tissue expressed IL-1RI, IL-1RII, IFN-alpha/beta R, M-CSFR, and SCFR. Of the 11 glioblastoma tissue specimens, IL-1RI was positive in 11, IL-1RII in 10, p75TNFR in nine, p55TNFR in nine, IFN-alpha/beta R in 10, IFN-gamma R in 10, GM-CSFR in two, G-CSFR in three, IL-8R in eight, and M-CSFR and SCFR in 11. These expressions were consistent with those in the cell lines, except for IL-8R. It is concluded that glioblastoma cells and normal astrocytes express a similar set of cytokine receptor genes in vitro and in vivo. Possible autocrine loops are suggested for IL-1 alpha/IL-1RI, TNF-alpha/p55TNFR, IFN-beta/IFN-alpha/beta R, M-CSF/M-CSFR, and SCF/SCFR in glioblastomas.
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PMID:Analysis of cytokine receptor messenger RNA expression in human glioblastoma cells and normal astrocytes by reverse-transcription polymerase chain reaction. 751 61


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