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

Tumour progression is a fundamental feature of the biology of cancer. Cancers do not arise de novo in their final form, but begin as small, indolent growths, which gradually acquire characteristics associated with malignancy. In the brain, for example, low-grade tumours (astrocytomas) evolve into faster growing, more dysplastic and invasive high-grade tumours (glioblastomas). To define the genetic events underlying brain tumour progression, we analysed the p53 gene in ten primary brain tumour pairs. Seven pairs consisted of tumours that were high grade both at presentation and recurrence (group A) and three pairs consisted of low-grade tumours that had progressed to higher grade tumours (group B). In group A pairs, four of the recurrent tumours contained a p53 gene mutation; in three of them, the same mutation was found in the primary tumour. In group B pairs, progression to high grade was associated with a p53 gene mutation. A subpopulation of cells were present in the low-grade tumours that contained the same p53 gene mutation predominant in the cells of the recurrent tumours that had progressed to glioblastoma. Thus, the histological progression of brain tumours was associated with a clonal expansion of cells that had previously acquired a mutation in the p53 gene, endowing them with a selective growth advantage. These experimental observations strongly support Nowell's clonal evolution model of tumour progression.
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PMID:Clonal expansion of p53 mutant cells is associated with brain tumour progression. 131 19

The aim of this study was to verify the tolerability and efficacy of therapeutic chemotherapy protocols, employing different combinations of cisplatin, carboplatin, etoposide and carmustine in primary glioblastoma patients. The purpose was focused on 2 end points: the response index to treatment, the TTP (tumor progression) and the ST (survival time). Eighty-four out of a group of 99 consecutive glioblastoma patients, entered this study. Patients were divided into 4 disparate treatment groups: (A) BCNU alone; (B) CDDP + VP-16; (C) CBDCA + BCNU; (D) CBDCA + BCNU + VP-16. The effectiveness and the TTP of the protocols differed, but differences were not statistically significant. Data concerning platinum treatment compare favorably with the best literature results. At 18 months more than half the carboplatin-treated patients are alive. Moreover these patients had a significantly longer ST than those treated with BCNU. We conclude that platinum-based chemotherapy has a beneficial effect on glial tumors.
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PMID:Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma. 148 54

Forty-five patients with malignant gliomas were treated after aggressive surgical resection with alternating intravenous carmustine and cisplatin both during and after radiation therapy. Thirty-three patients were considered evaluable for responses, 17 had glioblastoma multiforme (GBM), 14 had anaplastic astrocytoma (AA) and 2 had anaplastic oligodendroglioma (AO). The median age of the evaluable patients was 47 years. The median time to tumor progression was 34.5 weeks, and the median survival for the entire group was 76 weeks. Early progression occurred more frequently in patients with glioblastoma than in those with AA or AO. Seventeen patients (55%) were alive at 18 months (6 GBM, 9 AA, 2 AO). Toxicity was mainly hematologic, otic and tolerable. The results suggest that further trial is warranted to assess the efficacy of alternating carmustine and cisplatin in conjunction with radiation therapy postoperatively in patients with malignant gliomas.
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PMID:Adjuvant chemotherapy with carmustine and cisplatin for patients with malignant gliomas. 156 Feb 58

Hydroxyurea has been used since the early 1970s to potentiate the effects of radiation in the treatment of primary gliomas. In the only randomized study, a statistically significant increase in time to tumor progression for glioblastoma patients was noted for those receiving hydroxyurea. In other studies, hydroxyurea has been used as a cell-cycle phase-specific agent to improve survival in patients with recurrent gliomas and, in combination with 5-fluorouracil, to increase cell kill and as a potential DNA polymerase inhibitor. Other protocols have used hydroxyurea during radiation therapy in medulloblastoma and in combination chemotherapy for metastatic brain tumors as well. While widely used in the treatment of primary and secondary brain tumors, hydroxyurea trials usually have not been randomized or otherwise controlled; most have been nonrandomized, phase II activity studies. With the conclusion of some current trials, it is conceivable that the use of hydroxyurea may be more clearly defined in the treatment of tumors affecting the nervous system.
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PMID:The place of hydroxyurea in the treatment of primary brain tumors. 164 55

Quantitative determination of human glioma-associated antigen in cerebrospinal fluids (CSFs) obtained from 66 patients with a variety of neurological diseases was performed by solid-phase radioimmunoassay with a monoclonal antibody (G-22). In this system, the minimum detectable amount of the antigen in the CSF was 8 ng/ml. It was demonstrated that CSF diagnosis of glioblastoma might be possible in the case of small tumors with a diameter of less than 2 cm. CSFs obtained from all 18 patients with glioma were positive and the level varied from 11.2 to 186.1 ng/ml. The antigen level in the cystic fluid of the tumor was higher than that in CSF. There was a tendency for the antigen level in CSF to be correlated with the tumor size and the type of histology. The malignant types of glioblastoma or medulloblastoma showed higher levels than the benign type of ependymoma and astrocytoma. Most types of non-gliomatous brain tumor were negative except immature teratoma, meningioma with central neurofibromatosis, and metastatic brain tumor from lung cancer. We also noted that tumor progression or regression of malignant glioma could be predicted by the monitoring of the antigen in the CSF.
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PMID:Radioimmunoassay of glioma-associated antigen in cerebrospinal fluid and its usefulness for the diagnosis and monitoring of human glioma. 191 50

The role of cytoreductive surgery alone as effective salvage therapy for immediate palliation and durable symptom-free remission was examined in 17 patients (six with astrocytoma, seven with anaplastic astrocytoma, and four with glioblastoma) who developed symptomatic tumor relapse after initial surgery and irradiation. Individuals with widely disseminated subependymal, bihemispheral, or brainstem involvement were excluded. After reoperation, patients with astrocytoma and anaplastic tumors have been observed for an average of 31 and 29 months, respectively. As of this writing, all 13 patients are alive without evidence of tumor progression. Three of the four patients with glioblastomas have died 5, 12, and 17 months after reoperation, respectively. The 14 surviving patients overall have a current average Karnofsky performance level of 95. The durability of surgically induced palliation alone, the safe limits of resectability, and the clinical features associated with a favorable surgical response have been examined. The results indicate that, in selected individuals, durable remissions can be achieved by adequate resection of symptomatic tumor mass.
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PMID:Surgery for glioma relapse. Factors that influence a favorable outcome. 245 23

The determination and comparison of genotypic combinations at genomic loci in constitutional and tumor tissues from patients with various types of cancer have defined the chromosomal locations of loci in which recessive mutations play a role in disease development. The predisposing nature of some of these mutant alleles is exemplified by studies of retinoblastoma and osteogenic sarcoma, two clinically associated diseases that share a pathogenetically causal predisposition mapping to 13q14. Genomic alteration of chromosome 10 is apparent in glioblastomas and mixed tumors of glioblastoma/astrocytoma grade III but not in homogeneous astrocytoma grades II or III; this suggests the definition of a locus involved in tumor progression and, perhaps, an approach to molecular genetic staging of tumors.
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PMID:Loss of heterozygosity in stages of malignancy. 266 35

One hundred one patients with glioblastoma were studied to evaluate the effect of the extent of surgical resection on the length and quality of life. Extensive removal of tumor was performed for 45 patients, while the remaining 56 patients underwent partial removal or biopsy of tumor. The median time to tumor progression and the median survival in the former patients were 18.0 months and 23.0 months, respectively, and, in the latter patients, 6.0 months and 10.0 months, respectively. More than 80% of Karnofsky rating was observed in 69% of the former patients. Extensive removal of glioblastoma would be associated with longer and better survival when compared to partial removal.
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PMID:[Surgical treatment on survival and quality of life in patients with supratentorial glioblastoma:]. 281 Jul 72

Comparison of constitutional and tumor genotypes at chromosomal loci defined by restriction fragment length alleles has proven useful in determining the genomic position and tissue specificity of recessive mutations that predispose to cancer (Hansen, M.F., and Cavenee, W.K. Cancer Res., 47:5518-5527, 1987). Here we have applied this approach to 53 unrelated patients with glial tumors of varying histological malignancy grade. Loss of constitutional heterozygosity for loci on chromosome 10 was observed in 28 of 29 tumors histologically classified as glioblastoma (malignancy grade IV) whereas no similar losses were observed in any of 22 gliomas of lower malignancy grade. Examination of restriction fragment length alleles on other chromosomes revealed that loss of sequences on chromosomes 13, 17, or 22 had occurred at nonrandom frequencies and in at least one instance of each malignancy grade of adult glioma. The tumors in which loss of constitutional heterozygosity was observed were composed of one or a mixture of glial cell subtypes displaying astrocytic, oligodendrocytic, and/or ependymal differentiation. These results demonstrate a close association of the loss of chromosome 10 sequences with the most malignant histological stage of glioma and that glioblastoma arises as the clonal expansion of an earlier staged precursor. Furthermore they suggest that glioblastoma is a common phenotypic and malignancy terminus for glial tumors of various cellular subtypes which is reached through a common molecular pathway. This approach which involves the identification of malignancy stage specific somatic losses of heterozygosity provides a genotypic, rather than phenotypic, analysis of tumor progression.
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PMID:Clonal genomic alterations in glioma malignancy stages. 290 Dec 88

The Neuro-oncology Service of the University of California Brain Tumor Research Center conducted a nonrandomized phase II study to evaluate, in patients with recurrent malignant glioma, the benefit of a four-drug combination (BFHM) consisting of carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea), 5-fluorouracil, hydroxyurea, and 6-mercaptopurine. There were 29 evaluable glioblastoma multiforme patients and 45 nonglioblastoma anaplastic glioma patients available for analysis. Tumor progression was analyzed as the primary study endpoint. Of the glioblastoma patients, 16 of 29 (55%) responded or stabilized on therapy; of the other anaplastic gliomas, 32 of 45 (71%) responded or stabilized. For patients who stabilized or responded to treatment, BFHM achieved a median time to tumor progression of 46 weeks with a 25th percentile time to tumor progression of 68 weeks for anaplastic gliomas and a median time to tumor progression of 23 weeks with a 25th percentile time to tumor progression of 36 weeks for glioblastoma multiforme patients. A Cox multivariate analysis demonstrated that age and Karnofsky score were important prognostic variables for these patients.
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PMID:Phase II study of combined carmustine, 5-fluorouracil, hydroxyurea, and 6-mercaptopurine (BFHM) for the treatment of malignant gliomas. 302 25


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