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

The treatment of patients with malignant gliomas is palliative and encompasses surgery, radiotherapy, and chemotherapy. Outcome measures have demonstrated improvement in both survival and neurologic performance in patients undergoing complete or near-complete tumor resection. After surgery, involved-field radiotherapy (radiotherapy administered to the tumor and to the tissue in a 3-cm radius surrounding the tumor) has been shown to further improve survival rates when given in a total dose of 6000-6500 cGy. Survival is further improved by the coadministration of the chemoradiopotentiator hydroxycarbamide (hydroxyurea). The role of adjuvant or boost stereotactic radiotherapy is unclear, despite its frequent use. In addition, adjuvant chemotherapy has been shown to improve survival rates in approximately one-quarter of patients with glioblastoma multiforme and in the majority of patients with anaplastic astrocytoma. No a priori method exists, however, to predict which patient will benefit from adjuvant chemotherapy. As a consequence, all physiological young patients with good performance status or limited neurologic disability are treated with chemotherapy. The best results of adjuvant chemotherapy are achieved with a nitrosourea chemotherapy, either carmustine (BCNU) or a combination of procarbazine and lomustine (CCNU) and vincristine, known as PCV-3 therapy. Salvage chemotherapy is reserved for patients with tumor progression, some of whom benefit from a re-operation. Occasional patients with recurrent gliomas may be palliated by stereotactic radiotherapy.
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PMID:Practical guidelines for the treatment of malignant gliomas. 949 45

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with "glioblastoma multiforme." We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as "short-term" for TTP of less than 6 months (n = 54), and "long-term" for TTP of more than 12 months (n = 52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastoma multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n = 7) or anaplastic oligoastrocytoma (WHO grade III, n = 2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only prognostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy.
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PMID:Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation. 1092 75

Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.
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PMID:Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. 1093 31

EMMPRIN (extracellular matrix metalloproteinase inducer), also called CD147, basigin or M6 in the human, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). In our study, we investigated expression of EMMPRIN in human normal brain and gliomas, since mouse basigin and chicken HT7, the species homologues of human EMMPRIN, are associated with neuronal interactions and normal blood-brain barrier function, respectively. EMMPRIN expression was detected in all samples of non-neoplastic brain and glioma tissues examined. However, expression levels of EMMPRIN mRNA and protein were significantly higher in gliomas than in non-neoplastic brain. Moreover, levels of mRNA expression and immunohistochemical staining correlated with tumor progression in gliomas: They were highest in the most malignant form of glioma, glioblastoma multiforme, followed by anaplastic astrocytoma and then low-grade astrocytoma. Also, immunolocalization revealed quite different distributions in non-neoplastic brain and glioma: EMMPRIN was demonstrated only in vascular endothelium in non-neoplastic regions of the brain, whereas it was present in tumor cells but not in proliferating blood vessels in malignant gliomas. These data indicate that an MMP inducer molecule EMMPRIN is differently expressed in human normal brain and gliomas and could be associated with astrocytoma progression. Possible mechanisms whereby glioma cell EMMPRIN could influence tumor progression will be discussed.
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PMID:Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas. 1096 35

Traditional prognostic indicators for astrocytic tumors include tumor size, type, and histologic grade. Data suggest that tumor growth fraction assessed by MIB-1 is an important predicator of survival. Cyclin A, like MIB-1, is a recently described specific marker of proliferation, detectable primarily in S phase of the cell cycle as it undergoes progression to G2 phase. Thirty-seven cases of astrocytic tumors--14 cases of World Health Organization grade 1 and 2 (low grade tumors), 8 cases of grade 3 (anaplastic astrocytoma), and 15 cases of grade 4 (glioblastoma multiforme)--were simultaneously evaluated using routine paraffin immunohistochemical methods with commercial antibodies against MIB-1 and cyclin A. The results were quantitated using a Cell Analysis System (CAS) 200 image analyzer. The mean percentage positive nuclear area for MIB-1 was 3.32% in grade 1 and 2, 19.27% in grade 3, and 24.00% in grade 4 astrocytic tumors. Cyclin A showed a similar pattern of positivity in the same cases: 2.84% in grade 1 and 2, 16.27% in grade 3, and 24.88% in grade 4 astrocytic tumors. The data suggest that both proliferation markers correlated significantly with histologic grade. Cyclin A appears to be as good an indicator of brain tumor proliferation as MIB-1. Because cyclin A is detectable primarily in the S phase of the cell cycle, the fraction of cells positive for cyclin A should allow for a more accurate indicator of tumor progression.
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PMID:Comparison of cyclin A and MIB-1 expression in astrocytic tumors using image-based cell analysis system. 1127 8

Differential gene expression in tumors often involves growth factors and extracellular matrix/basement membrane components. Here, 11,000- gene microarray was used to identify gene expression profiles in brain tumors including high-grade gliomas [glioblastoma multiforme (GBM) and anaplastic astrocytoma], low-grade astrocytomas, or benign extra-axial brain tumors (meningioma) in comparison with normal brain tissue. Histologically normal tissues adjacent to GBMs were also studied. All GBMs studied overexpressed 14 known genes compared with normal human brain tissue. Overexpressed genes belonged to two broad groups: (a) growth factor-related genes; and (b) structural/extracellular matrix-related genes. For most of these 14 genes, expression levels were lower in low-grade astrocytoma than in GBM and were barely detectable in normal brain. Despite normal-appearing histology, gene expression patterns of tissues immediately adjacent to GBM were similar to those of their respective primary GBMs. Two genes were consistently up-regulated in both high-grade and low-grade gliomas, as well as in histologically normal tissues adjacent to GBMs. These genes coded for the epidermal growth factor receptor (previously reported to be overexpressed in gliomas) and for the alpha4 chain of laminin, a major blood vessel basement membrane component. Changes in expression of this laminin chain have not been previously associated with malignant tumors. Overexpression of laminin alpha4 chain in GBM and astrocytoma grade II by gene microarray analysis was confirmed by semiquantitive reverse transcription-PCR and immunohistochemistry. Importantly, an alpha4 chain-containing laminin isoform, laminin-8 (alpha4beta1gamma1), was expressed mainly in blood vessel walls of GBMs and histologically normal tissues adjacent to GBMs, whereas another alpha4 chain-containing laminin isoform, laminin-9 (alpha4beta2gamma1), was expressed mainly in blood vessel walls of low-grade tumors and normal brain. GBMs that overexpressed laminin-8 had a shorter mean time to tumor recurrence (4.3 months) than GBMs with overexpression of laminin-9 (9.7 months, P = 0.0007). Up-regulation of alpha4 chain-containing laminins could be important for the development of glioma-induced neovascularization and glial tumor progression. Overexpression of laminin-8 may be predictive of glioma recurrence.
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PMID:Overexpression of alpha4 chain-containing laminins in human glial tumors identified by gene microarray analysis. 1145 14

Among the entire spectrum of astrocytic neoplasms, just anaplastic astrocytoma (or grade III astrocytoma) appears to be a more enigmatic tumor entity with vague criteria for pathological diagnosis, unclear biological behavior and diverse clinical outcome. Attempts have been made to identify biological markers that would be useful in prediction of prognosis of anaplastic astrocytomas but the results obtained are controversial. In the present study, survival data on 63 patients with anaplastic astrocytoma were studied to evaluate a possible association between clinical outcome and expression of some immunohistochemical variables. Both the progression-free (PFS) and overall (OS) survival times were significantly reduced for patients older than 45 years, for anaplastic astrocytomas containing multiple mitoses, for Ki-67 LI > 5%, for cyclin A LI > 4% and for PTEN-negative tumors. We found no differences in survival times in patients with or without p53 immunoreactivity and also in cases with different values of p16 and p27 immunostaining. Multivariate analysis revealed that risk of tumor progression and death is independently associated with tumors containing multiple mitoses and for PTEN-negative tumors. According to the data from the CART modeling, tumors were subdivided based on the three following subsets: (1) Anaplastic astrocytomas with solitary mitosis. (2) Anaplastic astrocytomas with multiple mitoses and PTEN positivity. (3) Anaplastic astrocytomas with multiple mitoses and PTEN negativity. Thus, the results obtained reveal the advantage of combined approach including evaluation of routine histological parameters and immunohistochemical variables for further clinical subdivision of anaplastic astrocytomas.
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PMID:Immunohistochemical markers for prognosis of anaplastic astrocytomas. 1218 56

Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15 min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68 +/- 14 days. The response rates (CR + PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.
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PMID:A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas. 1262 55

The impact of various clinical pretreatment prognostic factors in patients with malignant glioma treated with a combined modality approach was investigated in 229 patients treated on four consecutive prospective phase II studies. The median survival time for all 229 patients is 14 months, and 2- and 5-year survival rates are 34%, and 9%, respectively. The median time to tumor progression is 14 months, and 2- and 5-year progression-free survival rates are 32%, and 9%, respectively. Females did better than males, while patients 55 years or less did better than those more than 55 years. Patients with Karnofsky performance status (KPS) 80 to 100 did better than those with KPS 50 to 70 as well as did patients having preoperative tumor sizes 4 cm or less when compared to those with larger tumors. Frontal tumor location as well as more extensive surgery favorably influenced survival. Patients harboring anaplastic astrocytoma fared significantly better than those with glioblastoma multiforme. Both univariate and multivariate Cox analyses confirmed independent influence of these prognosticators. When progression-free survival was used as an endpoint, all seven variables remained independent prognosticators. This study showed that sex, age, KPS, tumor size, tumor location, histology, and extent of surgery are independent prognosticators in patients with malignant glioma treated with combined modality approach.
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PMID:Clinical prognostic factors in patients with malignant glioma treated with combined modality approach. 1505 61

This is a pilot study performed to determine the maximum tolerated number of courses of high-dose thiotepa and carboplatin with autologous peripheral blood progenitor cell (PBPC) transplantation in poor-risk pediatric central nervous system (CNS) tumor patients. Twelve patients were enrolled and a total of 24 PBPC transplants were performed. The median age was 7.7 years. All patients had CNS tumors: 4 relapsed CNS PNET, 2 high-risk PNET in first remission, 2 relapsed/progressive brainstem tumor, 2 relapsed/progressive anaplastic astrocytoma, 1 relapsed GBM, and 1 recurrent ependymoma. The regimen consisted of thiotepa 250 mg/m2/day x 3 days and carboplatin 400 mg/m2/day x 3 days. No toxic deaths occurred. All patients were hospitalized for a median duration of 17 days. The median number of CD34 cells infused was 5.4 x 10(6)/kg (2.1-29.7 x 10(6)/kg) per course. Median time to ANC > 0.5 x 10(9)/L was 9 days, and platelets > 20 x 10(9)/L was 13.5 days. Four patients came off protocol after only one course of PBPC (2 had tumor progression, 2 parental choice); 4 patients underwent two, and 4 patients three courses of PBPC. Major nonhematologic complications were mucositis that necessitated infusion of narcotics (11/24 courses), fever of unknown origin (12/24), documented infection (9/24), and hemorrhagic cystitis (3/24). TPN was administered during 22 of 24 courses with a median duration of 15 days. It isfeasible to administer 2-3 courses of tandem high-dose thiotepa and carboplatin with PBPC transplant with prompt engraftment and manageable toxicities in pediatric CNS tumor patients.
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PMID:A pilot trial of tandem autologous peripheral blood progenitor cell transplantation following high-dose thiotepa and carboplatin in children with poor-risk central nervous system tumors. 1562 20


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