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)

This paper describes Phase I clinical studies of Antineoplaston A2 injections. The studies involved 15 patients diagnosed with advanced neoplastic diseases including cancers of the breast, bladder, lung, kidney, oesophagus, colon and liver, mesothelioma and glioma. Antineoplaston A2 was administered in divided doses daily intravenously through a subclavian vein catheter. The treatment was given from 53 to 358 days. The highest dosage administered was 147 mg/kg/24 h. Only minimal adverse effects were noticed sometime during the treatment, including fever, chills and myalgia. Desirable side-effects included increase of platelet and white blood cell counts, hypertrophy of epidermis and decrease of cholesterol and triglyceride levels. Nine patients showed objective response to the treatment. Cases of complete remission included adenocarcinoma of the lung, mesothelioma, metastatic liver and bladder cancers. In an additional case of breast cancer, the patient obtained complete remission of liver metastasis and stabilization of bone metastases. Partial remission was accomplished in cancers of the breast and oesophagus. Three patients, including cases of adenocarcinoma of the lung, mesothelioma and bladder cancer, were in complete remission for over five years.
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PMID:Initial clinical study with antineoplaston A2 injections in cancer patients with five years' follow-up. 356 10

The authors studied 24 patients affected by anaplastic gliomas in regard to the killer (Antibody-Dependent Cellular Cytotoxicity) and natural killer (Spontaneous Lymphocyte-Mediated Cytotoxicity) immunological functions, by counting the Cr51 release in Change liver and K 562 cell cultures, respectively. These parameters were also evaluated in 24 healthy donors as control, in 24 patients affected by bladder cancer and in nine cases of kidney cancer. Our data show, pre-operatively, a statistically significant impairment of ADCC and SLMC activity in glioma patients as compared both with controls, bladder and kidney cancer patients. The particular impairment of K and NK functions in gliomas is discussed with regard to the specific features of Central Nervous System malignancies. An improvement of ADCC activity was also found in the post-operative samples. This finding confirms other reports about partial restoring of altered immunocompetence after surgery, suggesting a link between extention of tumor mass and impaired immunological reactions.
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PMID:Particular features of cell-mediated immunity in patients with anaplastic gliomas. A comparison with kidney and bladder cancer patients. 608 20

The authors studied 24 patients affected by anaplastic gliomas, as regards immunology. In all of them the authors evaluated the lymphocyte subpopulation (B and T), firstly by simple lymphocyte count, secondly by studying the rosettes E-total and EAC, thirdly by stimulating the lymphocytes with mitogens phyto-haemoagglutinin-P (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM), and lastly by counting the release of Cr51 in Chang liver cells culture in order to obtain antibody dependent cellular cytotoxicity (ADCC). The parameters were also evaluated after surgery and during conventional radio-chemotherapy with BCNU. Whereas the so-called B-pool seems to be unaffected, the preliminary results show that the T-pool (identified by the E-t rosettes and by responses to PHA, PWM, and ConA) is depressed to a statistically significant degree, if compared with a control group. This depression seems to be related to the tumoral mass, and it is not increased by radio-chemotherapy. In addition, ADCC also seems to be depressed in our glioma patients in comparison with a control group and witha group of bladder cancer patients.
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PMID:Immunological monitoring of patients affected by anaplastic glioma concerning in effects of surgery, radio-, and chemotherapy. A preliminary report. 705 3

Interstitial deletions of the short arm of chromosome 9 are associated with glioma, acute lymphoblastic leukemia, melanoma, mesothelioma, lung cancer, and bladder cancer. The distal breakpoints of the deletions (in relation to the centromere) in 14 glioma and leukemia cell lines have been mapped within the 400 kb IFN gene cluster located at band 9p21. To obtain information about the mechanism of these deletions, we have isolated and analyzed the nucleotide sequences at the breakpoint junctions in two glioma-derived cell lines. The A1235 cell line has a complex rearrangement of chromosome 9, including a deletion and an inversion that results in two breakpoint junctions. Both breakpoints of the distal inversion junction occurred within AT-rich regions. In the A172 cell line, a tandem heptamer repeat was found on either side of the deletion breakpoint junction. The distal breakpoint occurred 5' of IFNA2; the 256 bp sequenced from the proximal side of the breakpoint revealed 95% homology to long interspersed nuclear elements. One- and two-base-pair overlaps were observed at these junctions. The possible role of sequence overlaps, and repetitive sequences, in the rearrangement is discussed.
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PMID:Breakpoint junctions of chromosome 9p deletions in two human glioma cell lines. 752 63

Deletions of chromosomal band 9p21 have been detected in various tumor types including melanoma, glioma, lung cancer, mesothelioma, and bladder cancer. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) has been proposed as a candidate tumor suppressor gene because it is frequently deleted in cell lines derived from multiple tumor types. We performed fluorescence in situ hybridization (FISH) with interphase cells using yeast artificial chromosome clones and a cosmid contig of the CDKN2 region. In 10 cell lines (4 glioma, 2 melanoma, 2 non-small cell lung cancer, 2 bladder cancer) with 9p alterations detected by molecular or cytogenetic analysis, interphase FISH with the CDKN2 cosmid contig detected all 9p deletions previously identified by molecular analysis. Using this probe, FISH analysis of primary glioblastoma tumors revealed homozygous deletions of the CDKN2 region in 6 of 9 tumors (67%) whereas a yeast artificial chromosome probe containing the interferon type I (IFN) gene cluster was deleted in only 4 cases (44%). Thus, it is likely that the CDKN2 region is the target of 9p deletions in gliomas. Interphase FISH will play an important role in defining the clinical significance of 9p deletions in primary tumors because it is especially applicable to clinical samples which may be contaminated by normal cells.
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PMID:Detection of CDKN2 deletions in tumor cell lines and primary glioma by interphase fluorescence in situ hybridization. 786 8

Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Experimental radioimmunotherapy. 849 64

The induction of glutamine starvation has been suggested as a potential target for antitumoral treatment using inhibitors of amidotransferase, an enzyme which mediates the conversion of glutamate to glutamine. Using multicellular aggregates from tumor cell lines, the effect of treatment with a suggested glutamine antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of treatment response, three different parameters were measured: aggregate size, uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the carcinoid cell line BON. In this cell line the maximum effect was reached already at 10 microM concentration. DON induced marked growth inhibition in the BON aggregates which lasted 3-4 weeks after which regrowth started. During this period the secretion of chromogranin and methionine uptake was also inhibited. These studies suggest that the neuroendocrine cell line BON is especially vulnerable to treatment by DON and show that strong inhibitory effects are found at concentrations lower than that achieved in patient blood in previous clinical trials.
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PMID:Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell aggregates. 925 48

The transcription factor E2F-1 drives cell cycle progression at the G1- to S-phase boundary; however, overexpression of E2F-1 can induce apoptosis. We show here that E2F-1 protein levels increase in human medulloblastoma, glioma, lung, colon, and bladder cancer cell lines (n=7) following treatment with the DNA damaging agents adriamycin or etoposide. This induction of E2F-1 occurs independently of Rb or p53 status and involves new protein synthesis. Although E2F-1 protein levels increase following DNA damage, several genes transcriptionally targeted by E2F-1 are not similarly induced. Rather, induction of E2F-1 in the tumor cells correlates with their sensitivity to adriamycin or to etoposide. Correspondingly, fibroblasts from E2F-1 knockout mice are more resistant to DNA damage than cells from normal mice. Overexpression of E2F-1 protein in tumor cell lines infected with an adenovirus encoding wild-type E2F-1 leads to enhanced cytotoxicity following exposure to DNA damaging agents, which results from enhanced apoptosis. The results of this study implicate a role for E2F-1 in p53-independent cytotoxicity of chemotherapy and provide a pharmacological tool for increasing levels of the apoptosis-inducing E2F-1 protein.
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PMID:p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin. 986 3

The tumour suppressor gene PTEN/MMAC1, which is mutated or homozygously deleted in glioma, breast and prostate cancer, is mapped to a region of 10q which shows loss of heterozygosity (LOH) in bladder cancer. We screened 123 bladder tumours for LOH in the region of PTEN. In 53 informative muscle invasive tumours (> or = pT2), allele loss was detected in 13 (24.5%) and allelic imbalance in four tumours (overall frequency 32%). LOH was found in four of 60 (6.6%) informative, non-invasive tumours (pTa/pT1). We screened 63 muscle invasive tumours for PTEN mutations by single-strand conformation polymorphism (SSCP) analysis and for homozygous deletion by duplex quantitative polymerase chain reaction (PCR). Two homozygous deletions were identified but no mutations. Of 15 bladder tumour cell lines analysed, three showed homozygous deletion of all or part of the PTEN gene, but none had mutations detectable by SSCP analysis. Our results indicate that PTEN is involved in the development of some bladder tumours. The low frequency of mutation of the retained allele in tumours with 10q23 LOH suggests that there may be another predominant mechanism of inactivation of the second allele, for example small intragenic deletions, that hemizygosity may be sufficient for phenotypic effect, or that there is another target gene at 10q23.
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PMID:Somatic mutation of PTEN in bladder carcinoma. 1036 Jun 73

The effect of tamoxifen on Ca(2+) signaling and viability in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Tamoxifen evoked a rise in cytosolic free Ca(2+) levels ([Ca(2+)](i)) concentration-dependently between 1 and 50 microM with an EC50 of 10 microM. The response was decreased by extracellular Ca(2+) removal. In Ca(2+)-free medium, pretreatment with 5 microM tamoxifen abolished the [Ca(2+)](i) increase induced by the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM), but pretreatment with brefeldin A (50 microM; a Ca(2+) mobilizer of the Golgi complex), thapsigargin (an inhibitor of the endoplasmic reticulum Ca(2+) pump), and carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler), only partly inhibited tamoxifen-induced [Ca(2+)](i) increases. This suggests that tamoxifen released Ca(2+) from multiple pools. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) rise after pretreatment with 5 microM tamoxifen in Ca(2+)-free medium. Inhibiting inositol 1,4,5-trisphosphate formation with the phospholipase C inhibitor U73122 (2 microM) did not alter 5 microM tamoxifen-induced Ca(2+) release. The [Ca(2+)](i) increase induced by 5 microM tamoxifen was not altered by La(3+), nifedipine, verapamil, or diltiazem. Tamoxifen (1-10 microM) decreased cell viability in a concentration- and time-dependent manner. Tamoxifen (5 microM) also increased [Ca(2+)](i) in neutrophils, bladder cancer cells, and prostate cancer cells from humans and glioma cells from rats. Collectively, it was found that tamoxifen increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from multiple Ca(2+) stores in a manner independent of the production of inositol 1,4, 5-trisphosphate and also by triggering Ca(2+) influx from extracellular space. The [Ca(2+)](i) increase was accompanied by cytotoxicity.
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PMID:Dual effect of tamoxifen, an anti-breast-cancer drug, on intracellular Ca(2+) and cytotoxicity in intact cells. 1100 Jan


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