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)

For the subgroup of patients with inoperable gastrointestinal stromal tumors, progress has been made by the rapid development and approval of the targeted therapy imatinib mesylate. Small round cell sarcoma, such as Ewing/PNET, desmoplastic small round cell sarcoma and rhabdomyosarcoma, are chemotherapy-sensitive and potentially curable malignancies, which are treated with multimodality, dose-intensitive and neoadjuvant protocols regardless of size or overt metastatic disease. A limited number of effective agents available for the treatment of patients with metastatic adult soft-tissue sarcoma exists, which have failed anthracyline and ifosfamide-based chemotherapy. Most other high-grade (grading >I) so-called adult-type soft-tissue sarcomas such as fibro, lipo, pleomorphic and synovial sarcoma are treated with a anthracycline-based regimen with or without ifosfamide as front-line therapy. In this review, the therapeutic activities of drugs currently available as second-line treatment in patients with metastatic soft tissue sarcoma are summarized, providing an overview of contentious or emerging treatment issues. In relapsed 'adult-type' soft-tissue sarcomas trofosfamide, gemcitabine and ecteinascidin (ET-743) appear to be drugs associated with moderate activity and an acceptable toxicity profile. An interesting finding to be noted is that the different drugs have particular effects in distinct subtypes of soft-tissue sarcoma; however, it has to be taken into account that the number of patients included in those phase II trials are limited. The role of the newer agents (e.g. patupilone derivates, brostallicin) is currently not definable. The so-called selective therapy targeting vascular endothelial growth factor (receptor), epidermal growth factor receptor, c-kit, Raf kinase or platelet-derived growth factor receptor and bcl-2 antisensing, proteasome, protein kinase C/B, and mammalian target of rabamycin inhibition will continue to be tested in gastrointestinal stromal tumors patients refractory to imatinib mesylate as well as in selected sarcoma subtypes.
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PMID:Systemic treatment options for patients with refractory adult-type sarcoma beyond anthracyclines. 1726 55

Melanocytic neuroectodermal tumor of infancy is a rare pigmented tumor generally occurring in the head and neck region in children 12 months of age or younger. The true incidence is unknown and fewer than 200 clinical case reports have been reported to date in the literature. The tumor itself is locally aggressive. It does not have a tendency to metastasize but carries a high risk of local recurrence. This report describes one patient's care, including primary palate reconstruction, and provides a review of the literature. A 7-month-old boy was found in a Haitian orphanage with a growing, very large mass originating from his right maxilla.
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PMID:Melanocytic neuroectodermal tumor of infancy: excision and primary palatal repair at 7 months of age. 1741 2

Ewing sarcoma/primitive neuroectodermal tumors (EWS/PNET) are characterized by specific chromosomal translocations most often generating a chimeric EWS/FLI-1 gene. Depending on the number of juxtaposed exons assembled, several fusion types have been described with different incidences and prognoses. To assess the impact of each fusion type on the specific phenotypic, tumorigenic, and metastatic features of EWS/PNET, we developed an amenable system using a murine mesenchymal multipotent C3H10T1/2 cell line. Upon transduction of EWS/FLI-1, cells acquired dramatic morphological changes in vitro, including a smaller size and "neurite-like" membrane elongations. Chimeric fusion proteins conferred oncogenic properties in vitro, including anchorage-independent growth and an increased rate of proliferation. Furthermore, EWS/FLI-1 expression blocked mineralization, with concomitant repression of osteoblastic genes, and induced a dramatic repression of the adipocytic differentiation program. Moreover, EWS/FLI-1 promoted an aberrant neural phenotype by the de novo expression of specific neural genes. The intramuscular injection of transduced cells led to tumor development and the induction of overt osteolytic lesions. Analogously, to what was observed in human tumors, type 2 EWS/FLI-1 cells formed primary tumors in immunodeficient mice with a higher incidence and a lower latency than cells bearing types 1 and 3 fusions. By contrast, cells expressing types 2 and 3 fusions showed specific metastatic activity with a higher number of macroscopic metastases in soft tissues and osteolytic lesions in the limbs as compared to type-1-expressing cells. Therefore, the structure of each oncoprotein strongly influenced its tumorigenicity and metastagenicity. Thus, this model provides a basis for understanding the genetic determinants involved in Ewing tumor development and metastatic activity and represents a cellular system to analyze other oncoproteins involved in human sarcomagenesis.
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PMID:EWS/FLI-1 oncoprotein subtypes impose different requirements for transformation and metastatic activity in a murine model. 1745 69

About 7 years ago, we undertook the resection on a patient with a tumour of the wall of the left ventricle near the atrioventricular junction. The pathologic diagnosis after the operation was peripheral primitive neuroectodermal tumour (pPNET) of the left ventricular wall. Microscopically the cell had a small, round, deeply basophilic nucleus, rich in chromatin, and little or no surrounding perikaryon. To our knowledge, no article has ever reported a case of primary myocardial PNET which grew towards the pericardial cavity and there is no adequate data on optimal treatment of PNET in the heart at present. In our case since the tumour recurred in situ and had no evidence of distant metastases, we considered orthotopic cardiac transplantation.
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PMID:Peripheral primitive neuroectodermal tumour of left ventricular wall origin: a rare case. 1798 77

We present the very unusual case of a young woman suffering from a brain tumor 22 years after a stage IV spinal neuroblastoma as an infant, demonstrating the difficulties of differentiating late neuroblastoma relapse from secondary supratentorial primitive neuroectodermal tumor (sPNET). Lacking specific immunohistochemical features, the first cerebral tumor at the age of 21 was regarded as sPNET, and we pursued a therapeutic approach consisting of neurosurgical resection as well as irradiation and high-dose alkylator-based chemotherapy according to the HIT2000 protocol. Two years later the patient suffered from a diffusely infiltrating local recurrence, changing its imaging appearance as well as its immunohistochemical characteristics, now revealing disseminated positivity for neuron-specific enolase and neural cell adhesion molecule. Moreover, the lack of PNET-specific translocations (EWS/FLI1 gene fusion) in both brain tumors as well as the development of hepatic metastases was more compatible with the diagnosis of a very late relapse 22 years after initial stage IV spinal neuroblastoma.
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PMID:CNS tumor 22 years after spinal neuroblastoma IV: diagnostic dilemma between recurrence and secondary malignancy. 1925 32

Olfactory neuroblastoma is an uncommon neuroectodermal tumor of the sinonasal tract. It represents 2% to 3% of sinonasal neoplasms. Most olfactory neuroblastoma behave locally aggressive with 30% recurrence rates. A subset metastasizes to lymph nodes and/or distant sites. Grading of olfactory neuroblastoma involves a combination of factors with low-grade tumors having better survival than high-grade tumors. The grade does not always predict prognosis, however, as metastases can be seen in all grades of olfactory neuroblastoma. Trk-A, Trk-B, and p75NRT are neurotrophin receptors associated with numerous solid malignancies, particularly pediatric neuroblastoma. GRP78 is an endoplasmic reticulum protein, associated with differentiation of neuroblastic cells. Trk-A, p75NRT, and GRP78 overexpression are favorable prognostic factors in pediatric neuroblastoma, whereas Trk-B is associated with a poorer prognosis in these tumors. Olfactory neuroblastoma is clinically distinct from pediatric neuroblastoma but shares some histological features. Trk-A and p75NRT have been demonstrated in olfactory neuroblastoma previously. Trk-B and GRP78 have not been investigated in olfactory neuroblastoma. None of these markers have been correlated with grade or outcome in olfactory neuroblastoma. To investigate the role of Trk-A, Trk-B, p75NRT, and GRP78, a series of 20 olfactory neuroblastomas was stained with these antibodies. Trk-A and Trk-B stained most cases of olfactory neuroblastoma (90% and 85%). GRP78 stained most cases (90%), although weakly. P75NRT demonstrated focal membranous staining in a sustentacular pattern (60%). None of these markers correlated with Hyams grade. None of these markers definitively correlated with patient outcome. Neurotrophin receptors do not appear to have a prognostic role; however, Trk's may play an oncogenic role in olfactory neuroblastoma.
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PMID:Expression patterns of Trk-A, Trk-B, GRP78, and p75NRT in olfactory neuroblastoma. 1938 45

Retinoblastoma is a relatively rare malignant pediatric tumor accounting for approximately 3% of childhood cancers and 1% of all cancer deaths in children under 15 years of age. During the clinical course of the disease, a metastasis usually occurs within the first year of diagnosis and is seen in 2% of retinoblastoma patients. Metastases to the intracranial region are common and account for approximately 50% of the metastatic cases. Metastasis to the soft tissue is very rare. Herein, we report a case of metastatic retinoblastoma presenting as a left shoulder soft tissue mass in a 14-year-old female with a 14-year history of familial bilateral retinoblastoma status post radiation therapy. In our case, the FNA cytology shows some features of the small round blue cell tumor group with inconspicuous Flexner-Wintersteiner or Homer-Right rosette formation. The unusual clinical presentation and morphology give rise to a diagnostic dilemma, with the differential diagnosis centering on the small round blue cell tumors such as lymphoma, rhabdomyosarcoma, nephroblastoma (Wilms' tumor), Ewing's sarcoma/PNET, and desmoplastic small round cell tumor. It also prompts concern for the development of a second primary tumor. The purpose of our study is to discuss the FNA cytology of metastatic retinoblastoma, its differential diagnoses, and the utility of immunohistochemistry. An accurate diagnosis is imperative due to the differences in prognosis and treatment implications for the various diseases.
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PMID:Metastatic retinoblastoma presenting as a left shoulder soft tissue mass: FNA findings and review of the literature. 1993 45

PNETs of the spinal cord are aggressive and local recurrence and/or leptomeningeal spread is common. Primary spinal PNETs are extremely rare and most cases involving the spinal cord are drop metastases from primary intracranial tumors by cerebrospinal fluid. Herewith, we present a 40-day-old infant with multilevel primary spinal PNET at Th12-L1 and L5-S1 levels associated with hydrocephalus occurring nearly 15 days after the operation. According to our knowledge this is probably the first case harboring all these pathologies. Multilevel primary intraspinal PNET in an infant is even rarer and can be associated with hydrocephalus that occurs during the postoperative period.
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PMID:Multilevel primary intraspinal PNETs in an infant associated with hydrocephalus. 2006 29

Surgical excision has been the mainstay of treatment for neuroendocrine tumors of the pancreas (PNET). Compounds like streptozocin and dacarbazin have been traditionally used in inoperable cases and somatostatin to treat syndromes deriving from functional tumors. However, a lot of progress has taken place in the area of molecular characterization of these tumors, revealing activation of mammalian target of rapamycin (mTOR) and VEGF pathways. Recent data from the 2010 ASCO Gastrointestinal Cancers Symposium demonstrate antitumor activity of everolimus, an mTOR inhibitor in combination with temozolomide in a phase I/II trial and of sunitinib versus placebo in a randomized double blinded phase III trial. The role of modern biologic compounds in the treatment of PNET is not clear yet. In addition, combination of resection and transarterial chemoembolization (TACE) has been proven effective over either modality alone in the treatment of PNET metastatic to the liver in a retrospective analysis. This comes to address the problem of selecting local intervention in a metastatic disease, which has been a reasonable choice for this group of tumors in the past. Last but not least the role of Ki-67 in decision-making in PNET is being discussed.
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PMID:Neuroendocrine tumors of the pancreas: what's new. Highlights from the "2010 ASCO Gastrointestinal Cancers Symposium". Orlando, FL, USA. January 22-24, 2010. 2020 21

Ewing's sarcoma is the second most common primary tumour of bone in childhood. Less frequently it occurs in soft tissues. Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) is an extra ordinarily rare primary tumour in the kidney. Only very few cases of primary renal Ewing's sarcoma have been reported in the literature to date. We present a case of primary right renal Ewing's sarcoma in a 13-year-old girl who was diagnosed as a case of stage IV ES/PNET of kidney with metastases to lung and liver. Right nephrectomy was done followed by adjuvant radiotherapy and chemotherapy with complete response to local and distant area.
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PMID:Ewing's sarcoma/PNET of kidney in 13-year-old girl. 2041 80


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