Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specimens of CSF from 76 children without neurologic disease and from 191 children with neurosurgical conditions were assayed for polyamine content. Putrescine and spermidine concentrations decreased with age. In children with intracranial tumors, polyamine concentrations in lumbar CSF were comparable with those in ventricular CSF. Putrescine level was significantly increased in children with medulloblastomas. Spermidine level was increased in children with medulloblastomas, glioblastomas, and astrocytomas. Concentrations of putrescine and spermidine were significantly increased in infants with myelomeningocele and hydrocephalus. Spermidine concentrations were significantly increased in older children with myelomeningocele, encephalocele, and hydrocephalus. Polyamines thus seem to be increased by rapid cell proliferation and by disorders affecting myelination. Since putrescine and spermidine concentrations may be of use in monitoring tumor progression, the effects of childhood growth and of hydrocephalus must be considered for children whose brain tumors are associated with hydrocephalus.
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PMID:CSF polyamines in childhood. 683 Apr 72

Pediatric brain gliomas are not always amenable for complete surgical excision, therefore adjuvant treatment for a large tumor mass is often required. As tumor volume shrinkage may not be a reliable method for assessing response to treatment, information about the tumor growth potential is desirable for an adequate follow-up of the patients. Choline (Cho) signal intensity, determined by proton magnetic resonance spectroscopy imaging (H-MRSI), has proved to be a reliable indicator of the metabolic activity and of tumor progression in various intracranial tumors. In this study we have sought to determine if H-MRSI can be of use in monitoring the response of pediatric gliomas to different forms of therapy. We performed pretreatment and post-treatment H-MRSI in 10 children with biopsed or partially excised brain gliomas. The follow-up period ranged between 6 and 40 months. A total of 38 H-MRSI were performed. All the patients had chemotherapy or radiotherapy. As an indicator of tumor activity we utilized the ratio between tumor/brain Cho signal intensity. Treatment response was evaluated as a function of tumor volume and clinical outcome. In 6 patients whose tumor volume decreased or remained stable we observed that the Cho ratio decreased (p < 0.01) after treatment and remained low during longitudinal follow-up. In the 4 patients whose tumors progressed the Cho ratio increased after treatment. These observations suggest that serial H-MRSI can provide valuable information regarding the response to therapy in pediatric gliomas and therefore be of use in the follow-up of these neoplasms of childhood.
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PMID:Variation of post-treatment H-MRSI choline intensity in pediatric gliomas. 1035 50

Intracranial germinoma has a relatively good prognosis when treated with radiotherapy and chemotherapy, whereas glioblastoma has a poor prognosis irrespective of these treatments. Cell proliferation and cell death are opposing processes in tumor growth, with tumor progression reflecting the balance between proliferating and apoptotic cells. We investigated cell proliferation and cell death using MIB-1 staining and nick-end labeling in 13 germinomas in comparison with 11 glioblastomas. Expression of BAX and Bcl-2, which regulate apoptosis, were studied by immunohistochemistry. Although germinomas showed strong MIB-1 immunostaining similar to that seen in glioblastomas, germinomas included significantly more apoptotic cells. The ratio of apoptotic ratio to MIB-1 labeling index for germinomas was 72.9 +/- 36.9 (mean +/- SD), a higher, statistically significant ratio as compared with glioblastomas (14.5 +/- 11.2; P < 0.01). Furthermore, germinomas showed greater expression of BAX than did glioblastomas, while the expression of Bcl-2 was weak in both tumor types. A comparison of these apoptotic-related proteins showed that immunoreactivity for BAX was relatively higher in germinomas than in glioblastomas (P < 0.01), corresponding well to numerous apoptotic cells identified in germinoma tissues. These findings may account for the prognostic difference between germinoma and glioblastoma in the face of a similar proliferation potential according to MIB-1 immunostaining. The balance between cell proliferation and death should be considered when predicting outcomes in patients with intracranial tumors.
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PMID:A comparative study of apoptosis and proliferation in germinoma and glioblastoma. 1130 26

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.
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PMID:Low-dose radiosurgery for benign intracranial lesions. 1290 78

Ependymomas are glial neoplasms whose clinical behavior is difficult to predict based on histology alone. Recently, a comparative genomic hybridization study identified frequent chromosome 9p and 13q losses in anaplastic ependymomas, suggesting that p16 and RB alterations may be involved in tumor progression. In order to test this hypothesis further, 101 myxopapillary, conventional, and anaplastic ependymomas (51 spinal and 50 intracranial tumors) were tested for RB and p16 deletions using fluorescence in situ hybridization. Clinical follow-up, ranging from 2 to 198 months (median 46 months), was obtained in 90 cases (91%). RB and p16 deletions were seen in 22 of 92 (24%) and 22 of 89 (25%) informative cases, respectively. Polysomies were more frequent in the grade I and II spinal tumors, consistent with prior reports of increased aneuploidy in such cases. No significant genetic associations were seen with tumor grade, recurrence, or death, suggesting that 9p and 13q deletions do not play a prominent role in the malignant progression of ependymomas, as has been implicated in other glioma subtypes.
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PMID:9p21 and 13q14 dosages in ependymomas. A clinicopathologic study of 101 cases. 1463 64

The hematopoietic growth factors granulocyte- and granulocyte-macrophage colony stimulating factor (G-CSF and GM-CSF) are nowadays widely used in routine cancer therapies as potent factors to control radiation and chemotherapy induced neutropenia, a side effect that frequently endangers the success of tumor therapies. However, there is little information about the role of G-CSF and GM-CSF for tumor growth or progression. We were interested in the expression and potential role of both factors in human meningiomas, tumors of arachnoidal origin that account for about 20% of all primary intracranial tumors. Therefore, we analyzed immunohistochemically the protein expression of G-CSF, GM-CSF and their respective receptors in 30 meningioma tissues of different malignancy and histopathological type. Both factors and receptors were not expressed in the corresponding normal tissue. In contrast, G-CSF, GM-CSF and their receptors were expressed to a varying degree in human meningiomas. Increasing expression of both factors and receptors correlated significantly with enhanced proliferation in the tumor and thus with higher malignancy. In addition, a strong perivascular expression of G-CSF was associated with a highly vascularized tumor type. Thus, expression of both G-CSF and GM-CSF is associated with the expression of proliferation vascularization, two markers of an increasingly malignant tumor phenotype, suggesting a contribution of both factors to tumor progression.
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PMID:Expression of G-CSF and GM-CSF in human meningiomas correlates with increased tumor proliferation and vascularization. 1521 49

RNA interference (RNAi) provides a powerful method for gene silencing in eukaryotic cells, including proliferating mammalian cells. Here, we determined whether RNAi could be utilized to inhibit the expression of proteases implicated in the extracellular matrix degradation, which is characteristic of tumor progression. We have previously shown that antisense stable clones of uPAR and cathepsin B were less invasive and did not form tumors when injected intracranially ex vivo. Since antisense-mediated gene silencing does not completely inhibit the translation of target mRNA and high molar concentrations of antisense molecules are required to achieve gene silencing, we used the RNAi approach to silence uPAR and cathepsin B in this study. We found that the expression of double-stranded RNA leads to the efficient and specific inhibition of endogenous uPAR and cathepsin B protein expression in glioma cell lines as determined by Western blotting. We also found the RNAi of uPAR and cathepsin B reduces glioma cell invasion and angiogenesis in in vitro and in vivo models. Intratumoral injections of plasmid vectors expressing hpRNA for uPAR and cathepsin B resulted in the regression of pre-established intracranial tumors. Further, RNAi for uPAR and cathepsin B inhibited cell proliferation and reduced the levels of pERK and pFAK compared to controls. Taken together, our findings indicate for the first time that RNAi operates in human glioma cells with potential application for cancer gene therapy.
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PMID:RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas. 1537 18

Since neural stem cells (NSCs) have the ability to migrate toward a tumor mass, genetically engineered NSCs were used for the treatment of gliomas. We first evaluated the "bystander effect" between NSCs transduced with the herpes simplex virus-thymidine kinase (HSVtk) gene (NSCtk) and C6 rat glioma cells under both in vitro and in vivo conditions. A potent bystander effect was observed in co-culture experiments of NSCtk and C6 cells. In the intracranial co-implantation experiments in athymic nude mice and Sprague-Dawley rats, the animals co-implanted with NSCtk and C6 cells and treated with ganciclovir (GCV) showed no intracranial tumors and survived more than 100 days, while those treated with physiological saline (PS) died of tumor progression. We next injected NSCtk cells into the pre-existing C6 tumor in rats and treated them with GCV or PS. The tumor volume was serially measured by magnetic resonance imaging. The tumor disappeared in six out of nine rats in the NSCtk/GCV group, while all the rats treated with PS died of tumor progression by day 21. The results indicate the feasibility of a novel gene therapy strategy for gliomas through a bystander effect generated by intratumoral injection of NSCtk cells and systemic GCV administration.
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PMID:Bystander effect-mediated gene therapy of gliomas using genetically engineered neural stem cells. 1577 95

Mouse glioma 261 (Gl261) cells are used frequently in experimental glioblastoma therapy; however, no detailed description of the Gl261 tumor model is available. Here we present that Gl261 cells carry point mutations in the K-ras and p53 genes. Basal major histocompatibility complex (MHC)I, but not MHCII, expression was detected in Gl261 cells. The introduction of interferon-gamma-encoding genes increased expression of both MHCI and MHCII. A low amount of B7-1 and B7-2 RNA was detected in wild-type cells, but cytokine production did not change expression levels. Gl261 cells were transduced efficiently by adenoviral vectors; the infectivity of retroviral vectors was limited. Low numbers of transplanted Gl261 cells formed both subcutaneous and intracranial tumors in C57BL/6 mice. The cells were moderately immunogenic: prevaccination of mice with irradiated tumor cells 7 days before intracranial tumor challenge prevented tumor formation in approximately 90% of mice. When vaccination was carried out on the day or 3 days after tumor challenge, no surviving animals could be found. In vitro-growing cells were radiosensitive: less than 2 Gy was required to achieve 50% cell mortality. Local tumor irradiation with 4 Gy X-rays in brain tumor-bearing mice slowed down tumor progression, but none of the mice were cured off the tumor. In conclusion, the Gl261 brain tumor model might be efficiently used to study the antitumor effects of various therapeutic modalities, but the moderate immunogenicity of the cells should be considered.
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PMID:Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. 1673 35

The diffuse, extensive infiltration of malignant gliomas into the surrounding normal brain is believed to rely on modification of the proteolysis of extracellular matrix components. Our previous results clearly demonstrate that uPA, uPAR and MMP-9 concentrations increase significantly during tumor progression and that tumor growth can be inhibited with antisense stable clones of these molecules. Because antisense-mediated gene silencing does not completely inhibit the translation of target mRNA and high concentrations of antisense molecules are required to achieve gene silencing, we used the RNAi approach to silence uPA, uPAR and MMP-9 in this study. We examined a cytomegalovirus (CMV) promoter-driven DNA-template approach to induce hairpin RNA (hpRNA)-triggered RNAi to inhibit uPA, uPAR and MMP-9 gene expression with a single construct. uPAR protein levels and enzymatic activity of uPA and MMP-9 were found to significantly decrease in cells transfected with a plasmid expressing hairpin siRNA for uPAR, uPA and MMP-9. pU(2)M-transfected SNB19 cells significantly decreased uPA, uPAR and MMP-9 expression compared to mock and EV/SV-transfected cells, determined by immunohistochemical analysis. Furthermore, the effect of the single constructs for these molecules was a specific inhibition of their respective protein levels, as demonstrated by immunohistochemical analysis. After transfection with a plasmid vector expressing dsRNA for uPA, uPAR and MMP-9, glioma-cell invasion was retarded compared with mock and EV/SV-treated groups, demonstrated by Matrigel-invasion assay and spheroid-invasion assay. Downregulation of uPA, uPAR and MMP-9 using RNAi inhibited angiogenesis in an in vitro (co-culture) model. Direct intratumoral injections of plasmid DNA expressing hpRNA for uPA, uPAR and MMP-9 significantly regressed pre-established intracranial tumors in nude mice. In addition, cells treated with RNAi for uPAR, uPA and MMP-9 showed reduced pERK levels compared with parental and EV/SV-treated SNB19 cells. Our results support the therapeutic potential of RNAi as a method for gene therapy in treating gliomas.
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PMID:Downregulation of uPA, uPAR and MMP-9 using small, interfering, hairpin RNA (siRNA) inhibits glioma cell invasion, angiogenesis and tumor growth. 1680 63


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