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)

Neck and back pain are frequent complaints of patients with pediatric cancer, second only to headaches as a cause of neurologic consultation. The importance of this symptom, however, has not been studied in the pediatric cancer patients. This report is a review of the consultations as a result of neck and back pain in patients with pediatric cancer, with analysis of clinical presentation, etiology, underlying cancer, and neuroradiologic findings. The etiology of the complaint varied with the underlying cancer, although metastatic disease to the spine was frequent in patients with solid tumors, in younger children, and in patients admitted to the hospital. Back or neck pain is a serious complaint in children with systemic cancer, because the incidence of metastatic disease is high. Magnetic resonance imaging of the whole spine should be obtained if metastatic disease can not be excluded clinically, particularly for young patients and in children with advanced disease.
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PMID:Back and neck pain in children with cancer. 1216 Sep 73

During the last two decades new diagnostic and therapeutic tools have been utilized to improve the poor survival chances of children with stage 4 neuroblastoma. This study reviews the risk profiles and the long-term outcome of patients from five consecutive German neuroblastoma trials. A total of 96% of all German patients registered at the German childhood cancer registry with neuroblastoma stage 4 over 1 year of age at diagnosis entered one of the trials during 1979-2001. Eight hundred and twenty-eight consecutive children were analyzed retrospectively. In spite of having significantly improved diagnostic tools like bone marrow superstaging and mIBG scintigraphy the stage 4 incidence did not increase after reaching completeness of the registry (5.4 cases/100,000 children at 1-14 years of age; P=0.52). The distribution of the primary tumors and of metastases was constant over the periods. The amount of bone marrow infiltration did not change with time. The risk factors lactate dehydrogenase, ferritin and MYCN, and the clinical risk groups 4A, 4B, 4C also remained constant over the trials with a few exceptions for NB97. The 5-year event free survival increased from 0.01+/-0.01 (NB79) to 0.14+/-0.03 (NB85), 0.16+/-0.04 (NB82), 0.27+/-0.02 (NB90), and 0.33+/-0.04 (NB97). The overall survival rates improved similarly from 0.04 (NB79) to 0.44 (NB97). In conclusion, the improved survival was associated with better treatment and not caused by lower risk profiles in stage 4 neuroblastoma patients.
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PMID:Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age. 1288 Sep 54

Wilms' tumour is a pediatric neoplasm exhibiting histologic features of developing kidney. Although the majority of Wilms' tumour patients are treated effectively, approximately 15% develop metastases and of these, 30% succumb to their disease. The biologic factors governing Wilms' tumour metastasis are largely unknown. Attempts at deriving representative Wilms' tumour cell lines, which could facilitate functional studies, have only been partially successful thus far. We now report on derivation and characterization of a Wilms' tumour cell line, WiT 49, from a first-generation xenograft of a human Wilms' tumour lung metastasis. WiT 49 recapitulates the phenotype of the parent tumours (primary and lung metastasis) and expresses normal WT1, overexpresses IGFII and carries a frequently identified p53 mutation. We recently reported overexpression of hepatocyte growth factor(HGF) and its receptor met in a series of Wilms' tumours with higher levels in homotypic metastatic cases. We therefore examined WiT 49 for expression of HGF/met and for met signaling targets associated with cell adhesion and cytoplasmic mediators of transcription using Western blot, co-immunoprecipitation, immunofluorescence labeling and zymography. Our results show co-expression of HGF and met protein, absence of E-cadherin, high levels of beta-catenin co-immunolocalized to met at the cell membrane and moderate levels of gamma-catenin and ezrin protein expression. After cell fractionation, beta-catenin was detected in the cytoplasm and nuclei of WiT 49 with relatively higher levels in the cytoplasm as compared to nuclei. Examination of MMP expression in WiT 49 showed constitutive activation of MMP 9 and latent MMP 2 supporting possible beta-catenin-mediated transcriptional activation. The WiT 49 cell line responded to recombinant human HGF by an increase in the expression of the met receptor, recruitment of the Gab-1 adapter protein to met and release of bound beta-catenin from met. Our studies therefore establish WiT 49 as a representative Wilms' tumour cell line derived from a lung metastasis that co-expresses HGF/met and shows absence of the cadherin-catenin complex supporting a role for these factors in regulation of the invasive and metastatic phenotype in Wilms' tumour.
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PMID:Derivation and characterization of a Wilms' tumour cell line, WiT 49. 1450 35

Metastatic cancers, once established, are the primary cause of mortality associated with cancer. Previously, we used a genomic approach to identify metastasis-associated genes in cancer. From this genomic data, we selected ezrin for further study based on its role in physically and functionally connecting the actin cytoskeleton to the cell membrane. In a mouse model of osteosarcoma, a highly metastatic pediatric cancer, we found ezrin to be necessary for metastasis. By imaging metastatic cells in the lungs of mice, we showed that ezrin expression provided an early survival advantage for cancer cells that reached the lung. AKT and MAPK phosphorylation and activity were reduced when ezrin protein was suppressed. Ezrin-mediated early metastatic survival was partially dependent on activation of MAPK, but not AKT. To define the relevance of ezrin in the biology of metastasis, beyond the founding mouse model, we examined ezrin expression in dogs that naturally developed osteosarcoma. High ezrin expression in dog tumors was associated with early development of metastases. Consistent with this data, we found a significant association between high ezrin expression and poor outcome in pediatric osteosarcoma patients.
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PMID:The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. 1470 91

Secondary malignancies are an important cause of morbidity and mortality in childhood cancer survivors. Salivary gland tumors account for about 6% of the second cancers. The majority of these are mucoepidermoid carcinomas (MEC) of the parotid gland. We report the clinical and pathological features of a rarer histological type, acinic cell carcinoma (ACC), in a childhood acute lymphoblastic leukemia (ALL) survivor. The behavior of secondary ACC appears similar to primary tumor and similar treatment may be adopted. Early recognition and complete resection is important for achieving a good outcome. Careful monitoring for recurrence or a third malignancy is needed.
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PMID:Parotid acinar cell carcinoma in a long-term survivor of childhood acute lymphoblastic leukemia. 1686 83

Neuroblastoma (NB) is a rapidly growing, well-vascularized childhood cancer that often presents with metastases. The overall five-year survival in NB is approximately 45% despite multimodality treatment, and therefore there is a clinical need for new therapeutic strategies. NB frequently overexpresses the angiogenic factor VEGF (vascular endothelial growth factor). The aim of this study was to investigate the effect of bevacizumab (Avastin, Genentech/Roche), a humanized anti-VEGF-A antibody, on NB growth in three different xenograft models, chosen to resemble high-risk NB. The human NB cell lines SK-N-AS, IMR-32 and SH-SY5Y, which are poorly differentiated and overexpress VEGF-A, were injected s.c. in immunodeficient mice. Bevacizumab was given intraperitoneally twice weekly at 5 mg/kg body weight, starting at a tumor volume of 0.3 mL. Bevacizumab significantly (p < 0.01-0.05) reduced NB growth in vivo without toxicity by causing a 30-63% reduction of angiogenesis, but had no effect on NB cell survival in vitro. Serum concentrations of VEGF-A increased two- to six-fold during bevacizumab therapy which did not result in faster tumor growth compared with control animals. Based on our experimental data we suggest consideration of bevacizumab in treatment of high-risk NB that does not respond to conventional therapy and that overexpresses VEGF.
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PMID:The anti-VEGF antibody bevacizumab potently reduces the growth rate of high-risk neuroblastoma xenografts. 1698 84

Over the last 2 decades, minimally invasive surgery (MIS) has become a significant tool for the diagnosis and treatment of malignant disease in adults. Despite initial reports of port-site metastases and peritoneal spread following laparoscopic resection of colorectal cancer in the 1990s, MIS is now commonly used for many applications in adult surgical oncology, including biopsy and resection of malignant disease in the chest and abdominal cavities, mediastinal and retroperitoneal lymph node dissection, staging of abdominal, pelvic and thoracic malignancies, and management of therapeutic complications. The use of MIS techniques in children is growing with the availability of smaller instruments and equipment more suitable to the pediatric patient. Herein, we review the role of MIS in the diagnosis, staging and treatment of malignant disease in children. We will also evaluate MIS as it applies to the palliation of disease and the management of treatment complications in childhood cancer.
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PMID:Minimally invasive surgery and childhood cancer. 1793 18

We retrospectively analysed the data of 70 patients (41 boys and 29 girls) with Rhabdoid tumors (RT) regardless of localisation, recorded in the German Childhood Cancer Registry (GCCR) from 1984 to 1999. The primary tumor was located in the kidney in 32 cases, in the central nervous system (CNS) in 13 cases and in the soft tissue in 25 cases. Variables examined were tumor stage, sex, age at diagnosis, surgical radicality, radiotherapy and chemotherapeutic regimens. Metastatic disease at diagnosis was observed in 18 of the 70 individuals. Outcome of this group was very poor with a 5-year overall survival of 11%. There were no differences in survival between males and females, or younger and older children. Chemotherapeutic regimens were mainly given according to the primary site of the tumor. Radiotherapy was given in 28 of the 70 patients with a mean dose of 35 Gray, though this did not improve the outcome. Overall survival of the whole cohort was 27% at 5 years and there was no significant difference in prognosis regarding the different locations of the tumor (kidney 24%, soft tissue 30%, CNS 29%). In conclusion, RT in infants and children has a dismal prognosis, independent from localisation. The presence of metastasis at diagnosis seems to be the only prognostic factor of outcome.
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PMID:Rhabdoid tumors in children: prognostic factors in 70 patients diagnosed in Germany. 1828 21

There is a dearth of information on the mortality of children with cancer in Nigeria but the few available reports suggest a poor outcome. The objectives of this study were to determine the underlying and immediate causes of death from childhood cancer. The mortality summary cards of all cases of childhood cancer seen at the Department of Paediatrics, University College Hospital, Ibadan between January 1998 and December 2004 were reviewed. Eighty-eight cases of childhood cancer were seen, out of whom 52 (59.1%) died, but only the 48 deaths with complete data were analyzed. These deaths comprised of 37 males and 11 females giving a male:female ratio of 3.4:1. Their ages ranged from 1 to 13 years with a mean of 7.3 +/- 3.4 years. The majority (71.4%) of all patients presented with diffuse or metastatic disease at diagnosis and this was associated with increased risk of dying. Of the 48 cases reviewed, 39 (81.3%) died without any remission of the primary tumour including 5 (10.4%) with disease progression despite treatment and 15 (31.3%) who died before treatment; only 4 cases (8.3%) died from tumour relapse. The immediate causes of death were infections (39.6%), bone marrow suppression (29.2%), treatment-related mortality (27.1%), organ failure (22.9%), bleeding (16.7%) and other metabolic causes (8.3%). Potentially reversible factors such as infections, bone marrow suppression and treatment-related events are the commonest causes of death from childhood cancer in Ibadan. Therefore, early presentation, prompt identification and effective management of these problems may reduce childhood cancer mortality in Nigeria.
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PMID:Causes of death in childhood cancer at the Department of Paediatrics, University College Hospital, Ibadan. 1875 49

Rhabdomyosarcoma (RMS) is a childhood cancer originating from skeletal muscle, and patient survival is poor in the presence of metastatic disease. Few determinants that regulate metastasis development have been identified. The receptor tyrosine kinase FGFR4 is highly expressed in RMS tissue, suggesting a role in tumorigenesis, although its functional importance has not been defined. Here, we report the identification of mutations in FGFR4 in human RMS tumors that lead to its activation and present evidence that it functions as an oncogene in RMS. Higher FGFR4 expression in RMS tumors was associated with advanced-stage cancer and poor survival, while FGFR4 knockdown in a human RMS cell line reduced tumor growth and experimental lung metastases when the cells were transplanted into mice. Moreover, 6 FGFR4 tyrosine kinase domain mutations were found among 7 of 94 (7.5%) primary human RMS tumors. The mutants K535 and E550 increased autophosphorylation, Stat3 signaling, tumor proliferation, and metastatic potential when expressed in a murine RMS cell line. These mutants also transformed NIH 3T3 cells and led to an enhanced metastatic phenotype. Finally, murine RMS cell lines expressing the K535 and E550 FGFR4 mutants were substantially more susceptible to apoptosis in the presence of a pharmacologic FGFR inhibitor than the control cell lines expressing the empty vector or wild-type FGFR4. Together, our results demonstrate that mutationally activated FGFR4 acts as an oncogene, and these are what we believe to be the first known mutations in a receptor tyrosine kinase in RMS. These findings support the potential therapeutic targeting of FGFR4 in RMS.
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PMID:Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models. 1980 59


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