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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gliomas, the most common brain tumors, are generally categorized into two lineages (astrocytic and oligodendrocytic) and further classified as low-grade (astrocytoma and oligodendroglioma), mid-grade (anaplastic astrocytoma and anaplastic oligodendroglioma), and high-grade (glioblastoma multiforme) based on morphological features. A strict classification scheme has limitations because a specific glioma can be at any stage of the continuum of cancer progression and may contain mixed features. Thus, a more comprehensive classification based on molecular signatures may reflect the biological nature of specific tumors more accurately. In this study, we used microarray technology to profile the gene expression of 49 human brain tumors and applied the k-nearest neighbor algorithm for classification. We first trained the classification gene set with 19 of the most typical glioma cases and selected a set of genes that provide the lowest cross-validation classification error with k=5. We then applied this gene set to the 30 remaining cases, including several that do not belong to gliomas such as atypical meningioma. The results showed that not only does the algorithm correctly classify most of the gliomas, but the detailed voting results also provide more subtle information regarding the molecular similarities to neighboring classes. For atypical meningioma, the voting was equally split among the four classes, indicating a difficulty in placement of meningioma into the four classes of gliomas. Thus, the actual voting results, which are typically used only to decide the winning class label in k-nearest neighbor algorithms, provide a useful method for gaining deeper insight into the stage of a tumor in the continuum of cancer development.
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PMID:Molecular voting for glioma classification reflecting heterogeneity in the continuum of cancer progression. 1607 69

The prognosis for patients with diffuse pontine gliomas (DPG) remains poor. New aggressive innovative treatments are necessary to treat this disease. From 1984 to 1998, eight patients (4M/4F), median age 11 years, with DPG were treated with monthly osmotic blood-brain barrier disruption (BBBD) chemotherapy using intraarterial carboplatin or methotrexate and intravenous cytoxan and etoposide. Patients presented for a median duration of 6 weeks with increased intracranial pressure, long tract signs, diplopia, ataxia, and nausea/vomiting. DPG was demonstrated on magnetic resonance (MR) imaging in seven patients and on CT in one. Two patients had biopsies that showed an astrocytoma and an anaplastic astrocytoma. Three tumors enhanced on MR imaging after contrast administration. Three patients had radiation therapy before BBBD chemotherapy and four afterwards. Two patients had chemotherapy (tamoxifen, topotecan) before BBBD chemotherapy and two afterwards. In general, patients were evaluated with MR imaging every 3 months to monitor for a response to treatment. The median number of chemotherapy cycles that were administered by BBBD was 10, mean 10. Three patients also received one, two, or three cycles of intraarterial chemotherapy without BBBD. One patient that was started on carboplatin was converted to methotrexate, and five that were started on the methotrexate protocol were later converted over to carboplatin. One patient received monthly methotrexate followed by 14 days of procarbazine and one patient started on methotrexate was switched to navelbine. MR imaging demonstrated two partial responses, five patients with stable disease, and one with disease progression. The median time to tumor progression was 15 months with the range from <1 to 40 months. The median survival from the time of diagnosis was 27 months, ranging from 7 to 80 months. The median survival time from the first BBBD or intraarterial treatment was 16.5 months, ranging from 5 to 69 months. One patient was lost to follow-up with an unknown date of death. Although the sample size is small, the TTP and survival times are longer than those previously reported in other DPG series. In addition, the ability to demonstrate stable disease or partial responses in DPG on MR imaging argues for the therapeutic benefit of BBBD chemotherapy. The enhanced delivery of chemotherapy afforded by osmotic BBBD supports the further examination of this treatment modality for patients with DPG.
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PMID:Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas. 1631 49

The case of a 12-year-old boy with anaplastic astrocytoma of the left thalamus is reported. Postoperative irradiation and chemotherapy could not repress tumor progression; therefore, treatment was undertaken with an oncolytic virus, MTH-68/H, an attenuated strain of Newcastle disease virus (NDV), and valproic acid (VPA), an antiepileptic drug, which also has antineoplastic properties. This treatment resulted in a far-reaching regression of the thalamic glioma, but 4 months later a new tumor manifestation, an extension of the thalamic tumor, appeared in the wall of the IVth ventricle, which required a second neurosurgical intervention. Under continuous MTH-68/H - VPA administration the thalamic tumor remained under control, but the rhombencephalic one progressed relentlessly and led to the fatal outcome. In the final stage, a third tumor manifestation appeared in the left temporal lobe. The possible reasons for the antagonistic behavior of the three manifestations of the same type of glioma to the initially most successful therapy are discussed. The comparative histological study of the thalamic and rhombencephalic tumor manifestations revealed that MTH-68/H treatment induces, similar to in vitro observations, a massive apoptotic tumor cell decline. In the rhombencephalic tumor, in and around the declining tumor cells, NDV antigen could be demonstrated immunohistochemically, and virus particles have been found in the cytoplasm of tumor cells at electron microscopic investigation. These findings document that the oncolytic effect of MTH-68/H treatment is the direct consequence of virus presence and replication in the neoplastic cells. This is the first demonstration of NDV constituents in an MTH-68/H -treated glioma.
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PMID:Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid. 1700 77

Pleomorphic xanthoastrocytoma (PXA) is a rare primary low-grade astrocytic tumor, recently classified as a neuroglial tumor. It generally occurs in children and young adults and shows benign behaviour (WHO II), although an anaplastic variant and malignant potential have been described. Pleomorphic xanthoastrocytomas with malignant transformation have been reported in three out of eight patients operated on for this type of tumor in our department in the last 15 years. The three patients were two adult women and a child, the primary tumors were located in the cortex of the right temporal lobe, and treatment consisted of complete surgical resection. Histological examination revealed simple PXA in two patients and a PXA with anaplastic foci in the other. Mean recurrence time was 5.7 years, with the original xanthoastrocytoma evolving to glioblastoma in two cases and anaplastic astrocytoma in the third. All three patients underwent a second operation, followed by adjuvant therapies. Two died from tumor progression and one from brain edema after intracerebral haemorrhage. A review of the available PXA literature dating back to 1979 revealed 16 cases of primary anaplastic astrocytoma and 21 cases of PXA with malignant transformation. Our experience adds three more cases of malignant transformations, outlining once again the potential malignancy of pleomorphic xanthoastrocytomas and the fact that prognosis in these cases is the same as for primary anaplastic astrocytoma and glioblastoma. Analysis of glioneuronal markers, Ki67 and p53 in all pleomorphic xanthoastrocytomas did not prove to be a discriminating factor to identify a subgroup of xanthoastrocytomas prone to malignancy. Accordingly, these tumors demand close long-term clinical and radiological follow-up.
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PMID:Malignant progression in pleomorphic xanthoastrocytoma: personal experience and review of the literature. 1718 43

Glioblastoma multiforme (GBM) develops from astrocytes and is the most aggressive primary cancer in humans. Invading cells grow rapidly and form their own blood vessels making them difficult to surgically remove or treat. GBM may develop de novo (primary) or through progression from a low-grade or anaplastic astrocytoma (secondary). Mutational inactivation of the p53 gene and presence of aberrant p53 expression are reported in GBM, suggesting that p53 has a role in tumor progression. This study of seven de novo GBM and four secondary GBM patients, indicated that nine out of eleven (82%) had overexpression of p53. Our histopathological analysis showed that the expression of p53 in three out of four (75%) secondary GBM was confined to the nucleus and the p53 positive cells were randomly distributed throughout the tumor. The expression of p53 in four out of seven (57%) de novo GBM was cytoplasmic, diffusive, and confined to the perivascular region of the tumor. In two (29%) de novo samples both nuclear as well as cytoplasmic staining that was not confined to the perivascular area was observed. The results suggest that cytoplasmic p53 may contribute to the formation and maintenance of de novo GBM by virtue of its control of the vasculature of tumors. Furthermore, cytoplasmic p53 may reflect an association of p53 with Cullin 7, PARC, or with the sequestering partner of p53, mortalin. These results underscore the significance of p53 in the tumorigenesis of de novo GBM.
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PMID:Revisiting the role of p53 in primary and secondary glioblastomas. 1721 19

Heparins represent the first choice for prevention and treatment of venous thromboembolism. In particular, low molecular weight heparins (LMWHs) provide pharmacokinetic advantages compared to unfractionated heparin (UFH): longer half-life, better bioavailability, and lower binding to plasma proteins. In the last years results of preclinical and clinical studies have suggested that LMWH may be able to inhibit cell growth, cell invasion, and angiogenesis, which are key mechanisms involved in tumor progression, possibly influencing favorable clinical outcome in at least a proportion of cancer patients. In this work we investigated the effect of LMWH (enoxaparin) on cell growth and cell invasion in primary cell cultures obtained from high-grade glioma specimens: 5 anaplastic astrocytoma (AA) and 13 glioblastoma multiforme (GBM). Apoptosis and expression of the thrombin receptor PAR1 were also assessed. A significant decrease in tumor cell growth was observed after treatment with 10 U/ml (-21%; p = 0.001) and 100 U/ml (-26%; p < 0.001); tumor cells from AA (grade III; WHO) were more affected by LMWH treatment compared to cell lines from GBM (grade IV; WHO). The antiproliferative effect was more pronounced in cell cultures displaying higher expression of PAR1. Glioma cell cultures were able to invade a model of basement membrane (Matrigel matrix) in standard culture conditions, but migration was not modulated significantly by LMWH treatment at any of the concentrations tested (1, 10, 100 U/ml). In conclusion, our results confirm the antineoplastic effect of LMWH, suggesting a potential direct role on tumor cell growth in high grade gliomas.
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PMID:In vitro study of low molecular weight heparin effect on cell growth and cell invasion in primary cell cultures of high-grade gliomas. 1729 5

Gliomas are the most common and deadly tumors in the central nervous system (CNS). In the course of studying the role of chemoattractant receptors in tumor growth and metastasis, we discovered that highly malignant human glioblastoma and anaplastic astrocytoma specimens were stained positively for the formylpeptide receptor (FPR), which is normally expressed in myeloid cells and accounts for their chemotaxis and activation induced by bacterial peptides. Screening of human glioma cell lines revealed that FPR was expressed selectively in glioma cell lines with a more highly malignant phenotype. FPR expressed in glioblastoma cell lines mediates cell chemotaxis, proliferation and production of an angiogenic factor, vascular endothelial growth factor (VEGF), in response to agonists released by necrotic tumor cells. Furthermore, FPR in glioblastoma cells activates the receptor for epidermal growth factor (EGFR) by increasing the phosphorylation of a selected tyrosine residue in the intracellular tail of EGFR. Thus, FPR hijacked by human glioblastoma cells exploits the function of EGFR to promote rapid tumor progression.
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PMID:Receptor "hijacking" by malignant glioma cells: a tactic for tumor progression. 1843 88

A retrospective study of bevacizumab only in adults with recurrent temozolomide (TMZ)-refractory anaplastic astrocytoma (AA) with a primary objective of determining progression free survival (PFS). There is no standard therapy for alkylator-resistant AA and hence a need exists for new therapies. Twenty-five patients (15 men; 10 women) ages 26-63 (median 50), with radiographically recurrent AA were treated. All patients had previously been treated with surgery, involved-field radiotherapy, and alkylator-based chemotherapy. Fourteen patients underwent repeat surgery. Patients were treated at second recurrence with bevacizumab (10 mg/kg), once every 2 weeks (defined as a single cycle). Neurological evaluation was performed every 2 weeks and neuroradiographic assessment following the initial two cycles of bevacizumab and subsequently after every four cycles of bevacizumab. All patients were evaluable for toxicity and response. A total of 360 cycles of bevacizumab (median 14 cycles; range 2-40) was administered. Bevacizumab-related toxicity included fatigue (14 patients; 2 grade 3), leukopenia (7; 1 grade 3), deep vein thrombosis (5; 2 grade 3), hypertension (5; 1 grade 3), anemia (4; 0 grade 3) and wound dehiscence (1; 1 grade 3). Sixteen patients (64%) demonstrated a partial radiographic response, 2 (8.0%) stable disease and 7 (28%) progressive disease following two cycles of bevacizumab. Time to tumor progression ranged from 1 to 20 months (median: 7). Survival ranged from 2 to 23 months (median: 9.0). 6-month and 12-month PFS were 60 and 20%, respectively. Bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent alkylator refractory AA.
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PMID:Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. 1895 91

The early appearance of high grade glioma on magnetic resonance (MR) imaging was retrospectively reviewed in the clinical records and MR images of 52 patients with intracerebral glioma treated in Osaka General Medical Center between 1997 and 2006. Three patients had no abnormal findings, and four patients had only hyperintense areas on T(2)-weighted imaging at initial MR examination. Five of the seven patients presented with generalized seizures. Six of the seven patients developed tumor progression within only 5 months. All patients underwent surgical tumor resection and the histological diagnoses were all high grade gliomas, glioblastomas in five, gliosarcoma in one, and anaplastic astrocytoma in one. Surveillance MR imaging should be performed at short intervals in adult patients presenting with seizures but with no or minimal abnormalities on initial MR imaging to identify progression of high grade glioma at the earliest opportunity.
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PMID:Early appearance of high grade glioma on magnetic resonance imaging. 1916 96

A recent study reported on mutations in the active site of the isocitrate dehydrogenase 1 (IDH1) gene in several types of gliomas. All mutations detected resulted in an amino acid exchange at position 132. We analyzed the genomic region spanning wild-type R132 of IDH1 by direct sequencing in 125 glial tumors. A total of 39 IDH1 mutations were observed. Mutations of the IDH2 gene, homologous to IDH1, were often detected in gliomas without IDH1 mutations. In the present study, R172 mutation of the IDH2 gene was detected in one anaplastic astrocytoma. IDH1 or IDH2 mutations were frequently in oligodendrogliomas (67%), anaplastic astrocytomas (62%), anaplastic oligoastrocytomas (75%), anaplastic oligodendrogliomas (50%), secondary glioblastomas (67%), gangliogliomas (38%), and anaplastic gangliogliomas (60%). Primary glioblastomas were characterized by a low frequency of mutations (5%) at amino acid position 132 of IDH1. Mutations of the IDH1 or IDH2 genes were significantly associated with improved outcome in patients with anaplastic astrocytomas. Our data suggest that IDH1 or IDH2 mutation plays a role in early tumor progression of several types of glioma and might arise from a common glial precursor. The infrequency of IDH1 mutation in primary glioblastomas revealed that these subtypes are genetically distinct entities from other glial tumors.
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PMID:Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. 1976


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