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)

Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a long history of human exposure. We now show that cinnamic acid induces cytostasis and a reversal of malignant properties of human tumor cells in vitro. The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using melanoma cells as a model, we found that cinnamic acid induces cell differentiation as evidenced by morphological changes and increased melanin production. Moreover, treated cells had reduced invasive capacity associated with modulation of expression of genes implicated in tumor metastasis (collagenase type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA-A3, class-I major histocompatibility antigen). Further molecular analysis indicated that the anti-tumor activity of cinnamic acid may be due in part to the inhibition of protein isoprenylation known to block mitogenic signal transduction. The results presented here identify cinnamic acid as a new member of the aromatic fatty acid class of differentiation-inducers with potential use in cancer intervention.
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PMID:Cinnamic acid: a natural product with potential use in cancer intervention. 762 77

Human solid tumors (prostate carcinomas PC-3 and DU-145, breast carcinoma MX-1, cervical carcinoma ME-180, small cell lung carcinoma SW2, and glioblastoma T98G) were grown as xenografts in nude mice. Using the Eppendorf pO2 histograph microelectrode system, the oxygen profiles of the tumors were determined while the animals breathed air or carbogen (95% O2/5% CO2), and after administration of the perfluorochemical emulsion Oxygent-CA (8 ml/kg) under air breathing and carbogen breathing conditions. Under normal air breathing with or without Oxygent-CA administration the mean oxygen tensions were between 4.9 and 9.3 mmHg and each tumor had severely hypoxic regions where the pO2 was less than 5 mmHg. The severely hypoxic regions comprised 41-71% of the oxygen tension measurements under normal air breathing conditions. Carbogen breathing alone increased the mean oxygen tensions to 10.9-23.9 mmHg. Administration of Oxygent-CA and carbogen breathing increased the mean oxygen tensions over the levels of carbogen breathing alone to varying degrees. The highest mean oxygen tensions were 40.8 mmHg in the T98G glioblastoma and 24.5 mmHg in the ME-180 cervical carcinoma. Investigation of the use of Oxygent-CA/carbogen to increase the oxygenation of clinical tumors is warranted.
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PMID:Oxygenation of human tumor xenografts in nude mice by a perfluorochemical emulsion and carbogen breathing. 784 46

We investigated the distribution of 111In-pentetreotide (Octreoscan, Mallinckrodt) in nude mice xenografted with a human neuroblastoma cell line (SKLAN, derived from the LAN1 line). These cells develop into solid tumours in nude mice and can be grafted repeatedly in grafts of 10(8) cells. Animals were sequentially explored by scintigraphy 2, 4, 24 and 48 hr after i.v. injection of 2.5-4 MBq of the tracer and killed at various times up to 48 hr. 111In-pentetreotide was rapidly and strongly taken up by all tumours, with a tumour/muscle (T/M) ratio on resected samples of 20.0 +/- 5.7 at 2 hr, 23.7 +/- 3.0 at 4 hr, 75.6 +/- 12.6 at 24 hr and 78.7 +/- 12.4 at 48 hr, for tumours ranging from 0.5 to 8 g. Scintigraphy results were quantitatively in agreement. Pre-injection of a 15-20 times larger quantity of unlabelled octreotide s.c. reduced the tumour uptake by a factor of 2. For comparison, nude mice xenografted with the same cell line were also studied with 123I-MIBG (4 MBq). At 24 hr, the T/M ratio was 0.62 +/- 0.18. Two other cell lines (glioblastoma ROM and small-cell lung carcinoma SC41) which were similarly tested with 111In-pentetreotide (2.5-4 MBq) gave T/M ratios at 24 hr of 4.8 +/- 2.8 and 38.4 +/- 21.8, respectively. Pentetreotide seems to have a high affinity for this MIBG-negative neuroblastoma cell line, which exhibited a clearly higher tumour uptake than the 2 other lines. This work provides new experimental arguments in favour of the particular interest of somatostatin analogues in neuroblastoma and confirms our first clinical results.
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PMID:Strong uptake of 111In-pentetreotide by an MIBG-negative, xenografted neuroblastoma. 790 95

Local invasive growth is one of the key features of primary malignant brain tumors accompanied by remodeling of the vasculature and destruction of normal brain tissue. Tissue invasiveness is an essential biological function used by a tumor to overcome the various barriers to its progression. The expression of metalloproteases has been shown to play a critical role in the invasive process in a number of tumors; however, their expression in human brain tumors has not been previously reported. In this study we showed metalloprotease activities at M(r) 240,000, 123,000, 92,000, 72,000, and 67,000 in brain tumor extracts. These enzyme activities were inhibited by EDTA, an inhibitor of metalloproteases. Significant increases in levels of protease bands at M(r) 92,000, 123,000, and 240,000 were observed in glioblastoma and metastatic lung tumors. Enzymatic inhibition and Western blotting with M(r) 92,000 type IV collagenase antibody confirmed the presence of M(r) 92,000 type IV collagenase in all samples. Quantitative analysis by densitometry showed 8-10-fold and 6-8-fold increases in M(r) 92,000 type IV collagenase activity in glioblastoma and metastatic lung carcinoma samples, respectively, when compared with normal brain, meningioma, astrocytoma, metastatic colon, and breast carcinoma samples. These findings provide evidence for elevated levels of metalloproteases in glioblastomas and suggest a therapeutic target for minimizing the invasive propensity of gliomas using protease inhibitors.
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PMID:Elevated levels of M(r) 92,000 type IV collagenase in human brain tumors. 848 4

The cytotoxic effects of short duration, high temperature, and long duration, low temperature hyperthermia were determined in human cells growing in culture. The human tumor cell lines A549 (lung carcinoma), WiDr (colon carcinoma), and U87MG (glioblastoma) were used. In addition, a normal human lung fibroblast cell type 18Lu was used. Sensitivity to direct cell killing was measured at 41, 43, and 45 degrees C. Heat induced perturbations of cell cycle and proliferation were also analyzed. The results obtained on sensitivity of the above human cell lines at 43 and 45 degrees C are similar to those of the previous work of others in that the human cell lines were observed to be relatively resistant to thermal killing at 43 or 45 degrees C, when compared to heat sensitive rodent cell lines. The comparison is important because most prior hyperthermic research has been performed with rodent cells and clinical protocols have been designed with the use of rodent data. In contrast to the 43 degrees C response, most of the human cells we tested were killed by 41 degrees C heating to an extent greater than that observed for rodent cells. The heat sensitivities of the four different human cell lines varied widely. This appeared to be due to differences in both intrinsic heat sensitivity and tolerance development. During 41 degrees C heating, human cells did not proliferate and cell cycle perturbations developed but did not correlate with sensitivity to killing. Our heat sensitivity measurements point out the shortcomings of using data derived from rodent systems to predict clinical outcome of hyperthermia therapy.
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PMID:Sensitivity of human cells to mild hyperthermia. 850 14

It is known that transfer of the wild-type p53 gene into p53-negative cells from transgenic mice increases their sensitivity to drug and radiation-induced apoptosis. However, unlike many human tumors, these transgenic cells do not express mutant p53, and it is not known from these earlier studies whether wild-type p53 dominates the effects of mutant p53 with respect to drug and radiation sensitivity. We addressed this question in glioblastoma, a disease characterized by an unusually high level of intrinsic resistance to therapy and poor prognosis: mean survival time from diagnosis is only about 1 yr. We introduced the gene for wild-type p53 into human T98G glioblastoma cells, which express endogenous mutant p53 but not wild-type p53. Stable transfectants that co-expressed mutant and wild-type p53 had enhanced sensitivity to cisplatin and gamma radiation, compared with parental cells, control vector-transduced cells, and transduced cells that had lost expression of wild-type p53. Transient wild-type p53 expression after high-efficiency gene transfer by a p53 adenovirus also sensitized the cells to cisplatin and correlated with the induction of apoptosis. The sensitization effect was also observed in p53 adenovirus-infected H23 small cell lung carcinoma cells, which express endogenous mutant p53. Therefore, wild-type p53 gene transfer has dominant effects over mutant p53 in sensitizing tumor cells to therapy, which supports the potential of p53 gene therapy to enhance the efficacy of traditional therapy.
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PMID:Use of wild-type p53 to achieve complete treatment sensitization of tumor cells expressing endogenous mutant p53. 851 17

Angiogenesis, the sprouting of new blood vessels from existing vessels, occurs in many physiological and pathological processes, including embryonic development, wound healing, and tumor growth. It is required for tumor growth because new blood vessel formation is necessary for tumors to expand beyond a minimum volume. Several growth factor receptor tyrosine kinases have been implicated in angiogenesis, including receptors for epidermal, fibroblast, and platelet-derived growth factors, as well as the receptors Flk-1/KDR, Flt-1 Tek/Tie-2, and Tie-1. Endothelial cells in the vessels of tumors express Flk-1/KDR, a receptor for vascular endothelial growth factor. Flk-1 was previously shown to play a role in angiogenesis and tumor formation of s.c. xenografts of C6 glioma cells using dominant-negative methodology. We now demonstrate that Flk-1 seems to be generally involved in the growth of a wide range of solid tumors, including mammary, ovarian, and lung carcinoma, as well as glioblastoma. Furthermore, survival times in rats bearing intracerebral tumors were prolonged using the same dominant-negative methodology. The involvement of Flk-1 in a variety of tumor types suggests an important role for Flk-1 in tumor angiogenesis.
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PMID:Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. 860 10

Empirical evidence in the clinical literature suggests that ionizing radiation influences human epileptic behavior. A group of patients with tumor-associated epilepsy, biopsy-proven malignancy, and primary antineoplastic treatment with ionizing radiation was selected to evaluate this observation. The antiepileptic effect of ionizing radiation was examined in 9 patients presenting with malignant cerebral tumor and medically refractory partial seizures during at least 2 months. Tissue diagnosis was obtained by stereotactic biopsy without further surgery. Histological categories included anaplastic astrocytoma (5 cases), glioblastoma (2), lymphoma (1), and metastatic non-small cell carcinoma of the lung (1). All patients had medically refractory simple partial seizures with or without secondary generalization with frequencies of 3/week to 8/day for 2-7 months before completion of therapy. Fractionated radiation therapy by parallel opposed fields was delivered with a cumulative dose range of 3,000-6,600 cGy. One patient also had 125I brachytherapy with implant removal after 6 months. Five patients had a seizure-free outcome for periods lasting 2-12 months, whereas the remainder experienced a reduction in frequency of greater than 75% during a follow-up period of 3 months to 6 years. One patient with a glioblastoma remained seizure-free for 3 months and experienced 2 generalized seizures during tumor progression and clinical deterioration but otherwise remained under good anticonvulsant control until his death after 1 year. This review of cases of partial seizures attributable to an unresected malignant cerebral tumor indicates that ionizing radiation may have a favorable effect upon medically refractory partial seizures with significant reduction or elimination of seizures. Moreover, the effect lasts beyond the immediate and early postradiation period. The therapy may thus also lessen the propensity for cerebral tissue towards later epileptogenicity that gives rise to a partial seizure disorder.
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PMID:Effect of ionizing radiation on partial seizures attributable to malignant cerebral tumors. 931 Oct 74

We present an unusual case of glioblastoma with intrathoracic and liver metastasis. The clinical diagnosis was confirmed by a percutaneous core needle biopsy from a metastatic lung lesion. The pathogenetic and diagnostic aspects of the case are discussed.
Lung Cancer 1998 May
PMID:Pleuropulmonary metastasis from an intracranial glioblastoma. 971 32

Although not structurally related, the pleiotropic cytokines interleukin-7 (IL-7) and interleukin-15 (IL-15) share a variety of biological functions including stimulation and maintenance of cellular immune responses. Cytokines, such as IL-7 or IL-15, elaborated by cells in situ, e.g. cancer cells, may be involved in shaping the quality of anti-tumor directed immune responses. We have analysed the constitutive and IFN-gamma-inducible expression of IL-15 or IL-7 mRNA, protein expression, and protein secretion in human tumor cell lines of distinct origin. IL-15 mRNA expression was detected in renal cell carcinoma (RCC), small cell lung carcinoma (SCLC), glioblastoma, neuroblastoma, mesothelioma cells and in EBV-transformed B-lymphocytes. IL-7-specific transcripts could be detected in colorectal cancer and in renal cell cancer cell lines. Immunohistochemical analysis demonstrated cytosolic IL-15 protein expression in renal cell cancer cells without apparent IL-15 protein secretion in vitro. Time kinetic analyses revealed that IFN-gamma mediated increase of IL-15 mRNA expression was transcriptionally regulated and dependent on de novo protein synthesis. However, enhanced IL-15 mRNA expression did not lead to effective protein secretion. In contrast, IL-7 mRNA expression in renal cell cancer or in colorectal cancer was associated with effective protein secretion which could be augmented by IFNgamma-treatment. These data suggest that both IL-7 and IL-15 mRNA are expressed in renal cell cancer, but exclusively IL-7 may be elaborated by tumor cells in situ. IL-15 regulation appears to be tightly controlled both at the transciptional and post-transcriptional level. Appropriate stimuli leading to effective IL-15 secretion from tumor cells may aid in modulating cellular immune responses directed against cancer.
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PMID:Constitutive and IFN-gamma regulated expression of IL-7 and IL-15 in human renal cell cancer. 986 5


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