Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Medulloblastoma is a highly malignant cerebellar tumor of children and, less frequently, of adults, with a tendency to early recurrence and dissemination through the cerebrospinal fluid. The prognosis has improved significantly in recent decades, in parallel with the improvement in neurosurgical techniques and the use of postoperative radiotherapy. An overview is given of the prognostic role of clinical and pathological features of individual cases as reported in the literature. Apart from the presence or absence of metastases at diagnosis and the radiotherapy modality, none of the factors studied was generally thought to have a definite significant prognostic role. The extent of surgical excision seems to influence survival more in pediatric cases than in adults. Ongoing cytogenetic studies and molecular biology investigations are aimed at better categorization of medulloblastomas and individualized postoperative treatment.
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PMID:Prognostic factors in medulloblastoma. 969 37

Medulloblastoma is the most frequent paediatric malignant brain tumour. The purpose of this study was to define imaging characteristics and contrast uptake patterns of primary and recurrent medulloblastoma using MRI. The MRI examinations of 17 histologically proven cases of medulloblastoma diagnosed in our institution (13 males and 4 females; mean age 13 years, 7 months) were reviewed in retrospect. Only patients with pre-treatment and follow-up examinations including T2-weighted images (fluid-attenuated inversion recovery or turbo spin echo) and T1-weighted images after contrast injection (0.1 mmol/kg Gd-DTPA) were included in this study. Whereas 6 of 7 tumours ( n=17) were hyperintense on T2-weighted images, contrast enhancement was detected in 13 patients. Fifteen tumours occurred in the cerebellar vermis, two were located in the cerebellar hemispheres. Mean size at the time of presentation was 30.1 mm. All patients presented with some extent of an occlusive hydrocephalus. Local recurrent tumour or metastases were seen in 6 patients (3 months to 7 years, mean age 2.5 years). Whereas the T2 signal intensity of recurrent tumour or subarachnoidal metastases resembled the primary neoplasms, the contrast uptake tended to be less pronounced ( n=3) or was completely absent ( n=2); thus, suggestive signs of primary medulloblastoma are location in the vermis, hyperintensity on T2-weighted images and hydrocephalus. The amount of contrast enhancement is variable and nonspecific. Secondary medulloblastoma manifestation is characterized by T2 hyperintensity but not by contrast uptake.
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PMID:MRI features of primary, secondary and metastatic medulloblastoma. 1204 37

Medulloblastoma is an infratentorial primitive neuroectodermal tumour. It is the most commonly occurring brain tumour of childhood, accounting for 15-20% of all paediatric tumours. Extracranial metastasis is rare, but may involve the skeleton. Jaw lesions, however, have never been described. A case is reported of metastases of a medulloblastoma to the jaw including the dental pulp.
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PMID:Metastatic infiltration of the dental pulp by medulloblastoma. 1207 30

Medulloblastoma (MB), the most common pediatric brain tumor, is a highly malignant disease with a 5-year survival rate of only 60%. Tumor cells invade surrounding tissue and disseminate through cerebral spinal fluid, making treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in tumor cells to support productive infection as an oncolytic virus. Here, we examined the ability of human reovirus to kill MB cells lines and surgical specimens in vitro and inhibit tumor growth/metastases in vivo. Most human MB cell lines tested (five of seven = 71.4%), two MB cell lines derived from spontaneously arising tumors in Patched-1(+/-) mice (two of two = 100%) and three MB primary cultures derived from surgical specimens, were susceptible to reovirus infection. Reovirus was internalized and transcribed in both susceptible and resistant cell lines. However, viral protein synthesis was restricted to cell lines with higher levels of activated Ras, suggesting that Ras plays a critical role in reovirus oncolysis in MB. Using an in vivo Daoy orthotopic animal model, we found that a single i.t. injection of reovirus dramatically prolonged survival compared with controls (160 versus 70 days, respectively; P = 0.0003). Repeating this experiment with GFP-labeled Daoy cells and multiple i.t. administrations of reovirus, we again found prolonged survival and a dramatic reduction in spinal and leptomeningeal metastases (66.7% in control injections versus 0.0% in the live virus group). These data suggest that this oncolytic virus may be a potentially effective novel therapy against human MB. Its ability to reduce metastases to the spinal cord could allow a reduction in the dose/field of total neuroaxis cerebral-spinal radiotherapy currently used to treat/prevent cerebral spinal fluid dissemination.
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PMID:Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma. 1281 Jun 44

Medulloblastoma in adults are rare and differ from their childhood counterparts in terms of tumor site (hemispheric location), histological subtype (desmoplastic variant), lower incidence of metastatic spread and frequent late relapses. As in children the presence of metastatic disease is of major prognostic significance. The role of different histological subtypes and molecular genetic/biological markers is unknown and deserves further investigations. The therapeutic strategies are essentially based on experiences in childhood medulloblastomas. Surgery followed by irradiation of the entire central nervous system followed by a boost to the posterior fossa is the cornerstones of treatment. A sufficient dose prescription and a high quality of treatment are a prerequisite for an optimal tumor control. Unlike in children the role of chemotherapy is an open question and requires prospective investigations. The forthcoming EORTC-study is addressing this issue.
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PMID:Current and future strategies in the management of medulloblastoma in adults. 1473 91

Medulloblastoma (MB) is the most common malignant brain tumor of childhood, yet it makes up only 1% of adult brain tumors. MB is uniquely sensitive to chemotherapy and radiation, but successful surgical resection continues to be an important component of therapeutic success. Progress in the treatment of MB has occurred in multiple areas from improved neurosurgical techniques, refined dosing and delivery of radiation, and optimized chemotherapy. Tumors are currently risk-stratified as average risk or high risk depending on clinical factors such as age, extent of resection, and presence of metastases. Molecular biology is beginning to improve upon clinical prognostication and may soon provide the means to accurately predict response to therapy. Treatment for average-risk MB has achieved a level of success that allows efforts to be focused on the limitation of adverse treatment effects. Therapy for high-risk and relapsed MB has been positively affected by the advent of high-dose chemotherapy with stem cell rescue. In addition, molecular targets are being elucidated and new therapeutic agents are being tested for safety and efficacy. Treatment for this disease has evolved a great deal over the preceding decades, but a great deal of work remains to be done to effect reliable cures while reducing long-term sequelae of therapy.
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PMID:Current treatment of medulloblastoma: recent advances and future challenges. 1549 20

Medulloblastoma is the most common malignant childhood brain tumor. Although some previous reports have shown up to a 70% 5-year survival for some of these patients, it is at the cost of significant long-term treatment-related morbidity. The cellular mechanisms leading to metastatic disease in medulloblastoma are mainly unknown. For the first time, we demonstrate the differential expression of heparanase in medulloblastomas and how these differences at the mRNA and protein levels affect the activity and invasive properties of three newly developed cell lines. Furthermore, heparanase expression was confirmed in 7 (88%) of 8 medulloblastoma clinical samples by immunohistochemical staining. Heparanase was found to be localized in the cytoplasm and nucleus. Quantitative polymerase chain reaction revealed a negative correlation between heparanase and TrkC (which is associated with a favorable clinical outcome). The activation of TrkC or TrkC/p75NTR by NT-3 affected heparanase activity and cell-invasive properties of medulloblastoma cells in vitro. Taken together, our data extend the body of evidence that invasion and expression/functionality of heparanase, in a context linked to TrkC and p75NTR, may play critical roles in the disease progression of medulloblastoma.
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PMID:Heparanase, TrkC and p75NTR: their functional involvement in human medulloblastoma cell invasion. 1607 9

Medulloblastoma is a rare malignancy in adults, accounting for approximately 1% of all primary brain tumors. Extraneural metastases have been reported in 10-30% of cases and most commonly involve bone; rarely lymph nodes, visceral organs and bone marrow may be involved with disease. We report here our experience with a 26 year-old woman with medulloblastoma treated with gross total resection followed by radiation therapy to her craniospinal axis. She subsequently developed widespread metastatic disease involving bone exclusive of the calvarium and spine for which multi-agent salvage chemotherapy was utilized with initial good clinical response. She later relapsed within the lymph nodes and soft tissues of the pelvis and eventually suffered a local recurrence within the posterior fossa. The treatment of medulloblastoma, particularly salvage therapy following disease recurrence, is reviewed.
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PMID:Extraneural metastatic medulloblastoma in an adult. 1659 30

Medulloblastoma (MB), the most devastating and common brain tumor in children, is highly invasive and extremely difficult to treat. Identifying the properties of MB tumors that cause them to invade and metastasize is therefore imperative for the development of novel treatments. We performed investigations to elucidate prognostic implications of heparanase (HPSE-1) and TrkC/p75(NTR) expression in MB using formalin-fixed, paraffin-embedded (FFPE) MB clinical specimens from children aged 1-19 years. Expressions of p75(NTR) and HPSE-1 correlated with each other (Pearson's correlation R = 0.899; P < 0.0001; R (2) = 81%; n = 14). In addition, TrkC:p75(NTR) ratios correlated with MB meningeal spread (R = 0.608; P = 0.0212; R (2) = 37%; n = 14). Secondly, using antibodies specific to TrkC and HPSE-1, we carried out immunohistochemistry (IHC) on 22 human MB tissue samples. IHC reaction scores revealed a significant expression of HPSE-1 in 76% of MB tissues from children aged 3 years and older (P = 0.0490; n = 17) while TrkC immunoreactivity was detected in 71% of these patient samples. Of note, TrkC was significantly present in 100% of MB female patients (P = 0.0313; n = 6). These studies support the role of p75(NTR) and HPSE-1 as two novel molecular determinants involved in the biology and clinical progression of MB.
Clin Exp Metastasis 2006
PMID:Heparanase expression and TrkC/p75NTR ratios in human medulloblastoma. 1682 29

Medulloblastoma is the most common malignant tumor of the cerebellum in children, with a tendency to metastasize via CSF pathway. Survival rate varies depending on several factors, but is rather favorable, with radiotherapy as the treatment of choice. Irradiation of the craniospinal axis results, however, in severe neuropsychological and psychosocial impairments pertaining to memory, attention, motor functioning, language, and visuospatial abilities. Precise mechanisms underlying the formation of medulloblastoma are still unclear, but implication of at least three signaling molecules is postulated: insulin-like growth factor-I, WNT, and Sonic hedgehog. Thanks to increasing knowledge on the cellular mechanisms contributing to tumor formation, it is possible to propose new therapies that could replace radiotherapy or allow decreasing irradiation doses. The current review presents recent developments in medulloblastoma pathophysiology research and proposed inhibitors that could constitute good candidates for further pharmacological research.
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PMID:Pathogenesis of medulloblastoma and current treatment outlook. 1708 11


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