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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma is a pediatric tumor that preferentially metastasizes to bone. Patients with bone metastases have a mortality rate >93%, indicating a need for novel treatment targets. Our laboratory has shown that type I insulin-like growth factor receptor (IGF-IR) expression and activation regulate neuroblastoma cell proliferation, motility, invasion, and survival, and that expression of the IGF-IR correlates with neuroblastoma tumorigenicity. Bone expresses large amounts of IGF ligands, and the IGF system is required for normal bone physiology. The current study addresses the role of the IGF system in neuroblastoma metastasis to bone. Upon reaching the bone marrow through the circulation, neuroblastoma cells must dock at the bone marrow endothelium, extravasate into the bone microenvironment, and destroy bone tissue to allow for tumor growth. This report examines the effects of high IGF-IR expression on neuroblastoma cell interaction with bone. The current data show that neuroblastoma cells with high IGF-IR expression, either endogenously or through transfection, adhere to human bone marrow endothelial cells and subsequently migrate toward both IGF-I and human bone stromal cells. High IGF-IR-expressing neuroblastoma cells adhere tightly to bone stromal cells, flatten, and extend processes. When neuroblastoma cells are injected directly into the tibiae of mice, those cells with increased IGF-IR form both osteolytic lesions within the tibiae and secondary tumors within other sites. These results support the hypothesis that IGF-IR expression in neuroblastoma cells increases tumor cell interaction with the bone microenvironment, resulting in greater formation of metastases.
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PMID:Insulin-like growth factor-I receptor expression regulates neuroblastoma metastasis to bone. 1681 29

Neuroblastoma (NB) is uncommon in the adolescent age group. It is located at any site containing sympathetic neural tissue, with retroperitoneal and adrenal lesions being the most common. Cutaneous and subcutaneous metastases of NB in children are infrequent. Primary thyroid NB with regional lymph node and distant multiple subcutaneous metastases was diagnosed in an 11-year-old boy. The differential diagnosis was primitive neuroectodermal tumor. Our case demonstrates the unique presentation of NB in an adolescent.
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PMID:The thyroid: an extremely rare primary site of neuroblastoma. 1694 5

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

Neuroblastoma is the second most common solid tumor in children that is metastatic in 70% of patients at the time of diagnosis. The ability of neuroblastoma cells to colonize distant organs like the bone marrow and the bone is the result of close interactions between tumor cells and the microenvironment. Significant progress has been recently made in our understanding of the mechanisms that promote the colonization and invasion of the bone by neuroblastoma cells and these mechanisms are reviewed in this article. How this understanding is now allowing us to test new therapeutic agents specifically targeted at interfering with neuroblastoma metastasis is then discussed.
Cancer Metastasis Rev 2006 Dec
PMID:Mechanisms of invasion and metastasis in human neuroblastoma. 1716 Jul 11

Neuroblastoma is a common pediatric malignancy that metastasizes to the liver, bone, and other organs. Children with metastatic disease have a less than 50% chance of survival with current treatments. Insulin-like growth factors (IGFs) stimulate neuroblastoma growth, survival, and motility, and are expressed by neuroblastoma cells and the tissues they invade. Thus, therapies that disrupt the effects of IGFs on neuroblastoma tumorigenesis may slow disease progression. We show that NVP-AEW541, a specific inhibitor of the IGF-I receptor (IGF-IR), potently inhibits neuroblastoma growth in vitro. Nordihydroguaiaretic acid (NDGA), a phenolic compound isolated from the creosote bush (Larrea divaricata), has anti-tumor properties against a number of malignancies, has been shown to inhibit the phosphorylation and activation of the IGF-IR in breast cancer cells, and is currently in Phase I trials for prostate cancer. In the present study in neuroblastoma, NDGA inhibits IGF-I-mediated activation of the IGF-IR and disrupts activation of ERK and Akt signaling pathways induced by IGF-I. NDGA inhibits growth of neuroblastoma cells and induces apoptosis at higher doses, causing IGF-I-resistant activation of caspase-3 and a large increase in the fraction of sub-G0 cells. In addition, NDGA inhibits the growth of xenografted human neuroblastoma tumors in nude mice. These results indicate that NDGA may be useful in the treatment of neuroblastoma and may function in part via disruption of IGF-IR signaling.
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PMID:Nordihydroguaiaretic acid inhibits insulin-like growth factor signaling, growth, and survival in human neuroblastoma cells. 1748 36

Neuroblastoma is the most common extracranial solid tumor of childhood. It commonly presents in children younger than 2 years of age, with 90% being younger than 5 years of age. There is marked variability in clinical behavior ranging from spontaneous regression or differentiation into benign tumors to rapid and progressive fatal disease. Approximately 50% of patients will have metastases at presentation. The management is dependent on age, stage of disease, and biological and biochemical markers. Nuclear medicine plays an important role in the initial staging, as a prognostic indicator, for assessment of response to treatment, and also in therapy. The most common nuclear medicine diagnostic studies are (99m)Tc-disphosphonate bone scintigraphy and (123)I-MIBG (metaiodobenzylguanidine) scintigraphy. Bone scintigraphy has been the main investigational modality to diagnose skeletal metastases. Whole body imaging with (123)I-MIBG has become the preferred diagnostic test because this agent accumulates in neuroblastoma in 90% to 95% of cases and will accumulate in the primary tumor and metastases particularly in bone, bone marrow, lymph nodes, and soft tissues. MIBG can be used to assess therapy response and is a significant prognostic indicator. Other diagnostic techniques include positron emission tomography (PET)/computed tomography, mainly using (18)F-fluorodeoxyglucose. Other more experimental PET agents, as well as radiolabeled antibodies and octreotide, also are being investigated. Therapy has mainly focused on palliation and has been used alone or in combination with chemotherapy in high-risk refractory or relapsed patients. Major attention is being placed on stratification of patients to try and reduce the side effects associated with intensive megatherapy in the low to intermediate risk patients. Neuroendocrine tumors (NETs) are rare in childhood, but nuclear medicine techniques, mainly using MIBG and somatostatin receptor agents, have a role in diagnosis, staging, and a limited role in therapy. Newer radiopharmaceuticals, including PET agents, are being evaluated for the assessment of NET. Nuclear medicine techniques play a major role in the management of neuroblastoma and NET.
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PMID:Neuroblastoma and other neuroendocrine tumors. 1754 28

Neuroblastoma is a tumor of the sympathetic ganglia and adrenal medulla that rarely metastasizes to the placenta. A 21-year-old gravida 3, para 1 at 28 weeks' gestation had an incidental finding of a 3.8-cm fetal renal mass on prenatal ultrasound. Within 1 week, the fetus developed hydrops and was delivered for nonreassuring fetal assessment. The mother developed mirror syndrome as manifested by hypertension, oliguria, and edema. The hydropic infant developed pulmonary hypertension, sepsis, and renal failure. On day of life 4, life support was discontinued. Pathological examination of the placenta revealed disseminated small round blue cells consistent with neuroblastoma. Metastasis of congenital neuroblastoma to the placenta is exceedingly rare, and cases discovered prenatally have resulted in significant maternal morbidity and 100% neonatal mortality.
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PMID:Mirror syndrome resulting from metastatic congenital neuroblastoma. 1758 17

Neuroblastoma is the most commonly occurring solid tumor in children. Most of these neoplasms are diagnosed within the first few years of life. The diagnosis of neuroblastoma may be difficult because of its ability to arise in different locations, its propensity to metastasize, and variable clinical signs and symptoms. Therefore, accurate and timely pathologic diagnosis is imperative. Herein, we present the rare description of an angiomatoid neuroblastoma. Only 1 other case has been previously reported.
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PMID:An unusual case of neuroblastoma with angiomatoid features. 1808 83

Neuroblastoma (NB) and Ewing sarcoma (ES) are neuroectodermal tumors typical of pediatric age that, despite aggressive treatment, still present a poor prognosis when in advanced stages. Studies indicate that c-KIT and platelet-derived growth factor receptor (PDGFR) play a substantial role in the proliferation and survival of NB and ES cells. Dasatinib, an oral multi-targeted inhibitor of several kinases including BCR-ABL and SRC-family kinases, is also active against c-KIT and PDGFR. Here, we evaluated the effect of dasatinib on the NB cell lines SJ-N-KP, SK-N-BE, AF8 and IMR5, and on the ES lines PDE02, TC106 and 6647. Proliferation and viability assays showed that dasatinib exerts an antiproliferative activity with a peak effect occurring at 24 h. After a 24-h exposure to dasatinib at 100 nM, proliferation was inhibited by 29.4+/-5.7% in SJ-N-KP, 41.3+/-11.7% in IMR5, 35.3+/-7.6% in PDE02 and 14+/-10.6% in 6647. Dasatinib did not induce apoptosis in NB and ES cell lines. A possible antimigratory activity of dasatinib was evaluated by scratch test. Dasatinib at 100 nM inhibited the migration of NB and ES cell lines by a mean of 30.2 and 25.3%, respectively. This activity suggests a possible role of dasatinib in inhibiting metastasis and appears of particular interest, given the association between metastatic disease and poor prognosis in these tumors. In conclusion, the cytostatic and antimigratory activity of dasatinib in NB and ES cell lines and the lack of pro-apoptotic activity suggests a possible use for this compound in the treatment of these tumors as a combination with other cytotoxic therapy.
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PMID:In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines. 1820 81

Neuroblastoma is often widespread at the time of diagnosis. Three physicians between 1900 and 1910 played an important role in the pathologic definition of neuroblastoma and its route of spread in relation to the age of the patient. These findings eventually led to the advances in treatment and decreased morbidity of today. In 1910 James Homer Wright was the first to recognize the tumor as being of primitive neural cell origin, calling it neuroblastoma and emphasizing the bundle of cells termed rosettes. While Wright recognized the neural nature of the tumor, the authors of previous reports had described its two distinct patterns of spread. In 1901 William Pepper published a series of infants with massive hepatic infiltration associated with adrenal tumors without spread to bone, and in 1907 Robert Grieve Hutchison reported his experience with a similar pathologic process in older infants and children who had orbital and skull metastases. Wright's valuable unifying concept served to tie together the descriptions of Pepper and Hutchison. A century later the names of these physicians should be remembered-Wright, who defined the adrenal tumor as of primitive neural origin, Pepper for his clinically accurate report of massive liver involvement in the infant, and Hutchison for describing the propensity of the tumor to spread to bone in older children.
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PMID:Neuroblastoma-remembering the three physicians who described it a century ago: James Homer Wright, William Pepper, and Robert Hutchison. 1903 43


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