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)

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

Rhabdomyosarcoma (RMS) are soft-tissue sarcoma commonly encountered in childhood. RMS cells can acquire invasive behavior and form metastases. The metastatic dissemination implicates many proteases among which are mu-calpain and m-calpain. Study of calpain expression and activity underline the deregulation of calpain activity in RMS. Analysis of kinetic characteristics of RMS cells, compared to human myoblasts LHCN-M2 cells, shows an important migration velocity in RMS cells. One of the major results of this study is the positive linear correlation between calpain activity and migration velocity presenting calpains as a marker of tumor aggressiveness. The RMS cytoskeleton is disorganized. Specifying the role of mu- and m-calpain using antisense oligonucleotides led to show that both calpains up-regulate alpha- and beta-actin in ARMS cells. Moreover, the invasive behavior of these cells is higher than that of LHCN-M2 cells. However, it is similar to that of non-treated LHCN-M2 cells, when calpains are inhibited. In summary, calpains may be involved in the anarchic adhesion, migration and invasion of RMS. The direct relationship between calpain activity and migration velocities or invasive behavior indicates that calpains could be considered as markers of tumor aggressiveness and as potential targets for limiting development of RMS tumor as well as their metastatic behavior.
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PMID:Calpains: markers of tumor aggressiveness? 2019 80

The purpose of this study was to determine patient characteristics and outcomes for bladder/prostate (BP) rhabdomyosarcoma (RMS) using an international cohort of prospectively treated patients comparing different treatment algorithms. Data were collected from 379 patients (1979-1998) treated on protocol; Intergroup Rhabdomyosarcoma Study, IRS-IV (n = 239 patients), International Society of Pediatric Oncology Malignant Mesenchymal Tumors (MMT) Committee MMT-84 and -89 (n = 74), Italian Cooperative Group, RMS-79 and RMS-88 Studies (n = 37) or German Cooperative Soft Tissue Sarcoma Study CWS-91 protocols (n = 29). A total of 322 (85%) patients had localized embryonal RMS (ERMS) and 27 had metastatic disease. Thirty patients (21 local disease; 9 metastatic) had nonembryonal BP RMS. Patients with localized ERMS had large tumors (64% >5 cm) that were invasive (54%) with uninvolved regional lymph nodes (N0, 93%). The 5-year failure-free survival (FFS) was 75% and the overall survival (OS) was 84%, with 89% of deaths attributed to disease. Treatment failures were usually local disease recurrence (60%). Predictors of FFS included T-stage (invasiveness), size, and histology. FFS was decreased for patients not receiving initial radiotherapy but this did not translate into a decreased OS. The 21 patients with localized nonembryonal BP RMS had a FFS and OS of 47%. The 36 patients with metastatic disease were more likely to be older and had large tumors that were invasive with alveolar histology and regional lymph node involvement. The 5-year FFS and OS were 41 and 44%, respectively. In conclusion, the majority of BP RMS patients had localized ERMS with a resultant good prognosis using current treatment algorithms. There were differences in FFS between treatment protocols but this did not result in an altered OS.
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PMID:Comparison of outcomes based on treatment algorithms for rhabdomyosarcoma of the bladder/prostate: combined results from the Children's Oncology Group, German Cooperative Soft Tissue Sarcoma Study, Italian Cooperative Group, and International Society of Pediatric Oncology Malignant Mesenchymal Tumors Committee. 2047 32

Rhabdomyosarcoma is a malignant tumor originating from rhabdomyoblasts that is rarely reported in domestic animals or in free-living and pet birds. This paper presents a case of rhabdomyosarcoma in a free-ranging yellow-headed caracara (Milvago chimachima), originating from the muscle region of proximal left humerus, with metastases in the left pectoral muscles, heart, lungs, and proventriculus. The cytology was suggestive of rhabdomyosarcoma because of malignant features and cytoplasmic cross-striations in cells. The histopathologic examination revealed neoplastic proliferation composed of spindle cells arranged in irregular sheets or bundles with marked cellular pleomorphism, moderate mitotic ratio, and multinucleated giant cells. Some neoplastic cells also presented evidence of scant cytoplasmic cross-striations visible at histologic sections stained by hematoxylin and eosin and phosphotungstic acid hematoxylin. Immunohistochemically, tumors cells were positive for desmin and negative for alpha-smooth muscle actin and S100 protein.
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PMID:Rhabdomyosarcoma in a yellow-headed caracara (Milvago chimachima). 2060 46

Rhabdomyosarcoma is a typical tumor of childhood, characterized by a high grade of malignancy, local invasiveness and a marked propensity to metastasize, but also a generally good response to chemotherapy and radiotherapy. Multimodal therapy is essential to cure rhabdomyosarcoma patients, but different uses of surgery, radiotherapy and chemotherapy, and their intensity, need to be selected and modulated to different patient risk groups. This article attempts to give an account of the current treatment options, the open and debated issues and the potential novel strategies for the near future.
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PMID:Selecting multimodal therapy for rhabdomyosarcoma. 2073 14

Rhabdomyosarcoma is a common malignant soft-tissue tumour in children, accounting for 6-7% of all malignant tumours in childhood. Congenital neoplasms are very rare in childhood and represent 2.5% of all paediatric tumours; the intrauterine or congenital diagnosis of rhabdomyosarcomas is extremely seldom. The most frequent locations of rhabdomyosarcomas are the head and neck regions. There are a number of ultrasonographic differential diagnoses. In cases of foetal rhabdomyosarcomas in utero, not only distant metastases but also the possibility of placental infiltration and thus of hypothetical distant metastases in the mother must be taken into consideration because of their metastatic potential. Only very few cases of transplacental penetration of tumour cells and especially of foeto-maternal metastatic invasion, in contrast to materno-foetal tumour cell transfer in the case of maternal cancer disease, have been reported in the literature. We report on a foetal rhabdomyosarcoma of the head and neck area with massive cardiac and placental infiltration associated with intrauterine foetal death in the second trimester. Sonographic features and necropsy findings are described and the differential diagnosis is discussed. Furthermore, diagnostic approaches to rule out a pattern of transplacental metastases are presented.
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PMID:[Foetal rhabdomyosarcoma with massive cardiac and placental infiltration associated with intrauterine foetal death]. 2080 52

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric and adolescent population. Though treatments for localized disease have reasonable long-term success rates, if disease is diffuse at diagnosis, outcomes are far poorer. Additional and/or alternative therapies are critical for improved clinical outcomes. One potentially therapeutic target is the signal transducer and activator of transcription 3 (STAT3) pathway. STAT3 has been shown to have constitutive activation in human rhabdomyosarcoma cells; thus, inhibition of STAT3 signaling may be a mechanism to induce tumor cell death. Celecoxib has been shown, by computer modeling, to bind STAT3 at the SH2 domain and competitively inhibit native peptide binding necessary for phosphorylation and subsequent propagation of the STAT3 signaling cascade. We found that celecoxib inhibits IL-6-induced and persistent STAT3 phosphorylation and inhibits cell viability in human rhabdomyosarcoma cells. We found that genes downstream of STAT3 (BCL-2, survivin, cyclin D1) were downregulated with celecoxib. Celecoxib also inhibits colony formation and cell migration. Our results suggest that, though known more commonly as a cyclooxygenase-2 (COX-2) inhibitor, celecoxib could act through the STAT3 pathway as well. More importantly, its effect on cell migration and clonogenic colony forming ability make it a potentially useful therapeutic agent for rhabdomyosarcoma, especially in metastatic disease whose clinical outcome is marginal at best with current therapies.
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PMID:Celecoxib inhibits STAT3 phosphorylation and suppresses cell migration and colony forming ability in rhabdomyosarcoma cells. 2139 87

Exophthalmus is the leading sign of space-occupying lesions of the orbit. Patients may further present with lid swelling, impaired ocular motility and optic neuropathy including a relative afferent pupillary defect, compressive optic disc edema or optic atrophy. Orbital tumors can be classified into various categories depending on the etiology, as lymphoproliferative lesions (in particular non-Hodgkin's lymphoma as the most common malignant orbital tumor of adulthood), optic nerve and meningeal lesions, lacrimal gland lesions, secondary orbital tumors which extend to the orbit from neighboring structures and metastases. Slightly less common are vasculogenic and cystic lesions including cavernous hemangioma as the most common benign orbital tumor of adulthood and dermoid cysts as the most common benign orbital tumor of childhood. Rhabdomyosarcoma is the most common malignant orbital tumor of childhood but has a low total incidence. Orbital tumors might not only cause symptoms like pain, diplopia and loss of visual acuity but may also lead to esthetically disfiguring changes. Particular attention should be paid to underlying systemic diseases and generalized tumor diseases. This article illustrates the approach to a detailed clinical and neuroradiological assessment which is mandatory for the care of orbital tumor patients.
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PMID:[Clinical and neuroradiological diagnostics of orbital tumors]. 2169 5

Rhabdomyosarcoma (RMS) is an aggressive malignant soft tissue tumor that arises from primitive striated muscle cells called rhabdomyoblasts. RMS is a rare tumor in adults, and involvement of the sinonasal area is extremely rare, comprising only 1.5% of all reported head and neck RMSs. Alveolar RMS, mainly seen in adults, has the worst prognosis. Incidence of lymph node metastases is more common in this type compared with the other forms. Fine needle aspiration cytology (FNAC) has been used extensively in the diagnosis of metastatic malignancies. However, metastatic soft tissue sarcomas are often overlooked, primarily due to the low frequency with which they occur. Here, we report a rare case of metastatic alveolar RMS in the cervical lymph nodes of an 18-year-old girl that was detected by FNAC. After 6 months, the patient came with a huge mass involving the nasal vestibule and the upper lip. Histology of both the main mass and the lymph nodes revealed alveolar RMS.
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PMID:Fine needle aspiration cytology of metastatic alveolar rhabdomyosarcoma. 2189 47

Rhabdomyosarcoma (RMS), which affects mainly pediatric patients, is currently classified into 3 major categories: embryonal, alveolar, and pleomorphic. We have identified a distinct variant of RMS that is characterized by epithelioid morphology, reminiscent of poorly differentiated carcinoma or melanoma, for which we propose the designation "epithelioid RMS." We examined the clinicopathologic features of 16 such cases, which were received in consultation between 1991 and 2009. Ten patients were men, and 5 were women (gender was unknown in 1 case), with a median age of 70.5 years (range 14 to 78). Primary anatomic sites were upper extremity (4), lower extremity (2), head and neck (3), trunk (3), hypopharynx (1), and left atrium (1). Two patients presented with nodal metastases (neck and mediastinal) with unknown primary sites. Of the tumors in somatic locations, 10 were intramuscular, and 2 were subcutaneous. Tumor size ranged from 3 to 8.5 cm; the tumors had nodular fleshy cut surfaces, grossly appreciable necrosis, and infiltrative edges. Microscopically, tumors showed sheet-like growth of uniformly sized epithelioid cells with abundant amphophilic-to-eosinophilic cytoplasm, large vesicular nuclei, and frequently prominent nucleoli. Necrosis and infiltration into adjacent structures (such as skeletal muscle or fat) were present in all cases, and mitotic counts were high (median count 23 per 10 high-power fields) with frequent atypical forms. By immunohistochemistry, all tumors showed diffuse desmin expression, and myf-4 immunostaining was diffuse to multifocally positive. S100-protein was absent in all cases. Cytokeratin was negative in 12 cases and very focally positive in 4 cases. Clinical follow-up information was available for 11 cases (median duration 10 mo). Most patients underwent surgical resection with chemotherapy and/or radiation (none with RMS-specific protocols). Two patients had multiple recurrences, and 2 patients developed satellite nodules near the primary lesion. Six patients had regional lymph node metastases, and 6 patients developed distant metastases, most commonly to the lung. So far, 7 patients have died of disease, 5 within 1 year and 2 within 5 years. Epithelioid RMS is a novel morphologically distinct variant of RMS that closely mimics carcinoma or melanoma. It primarily affects older patients, with a male predilection. The clinical course as determined thus far is aggressive.
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PMID:Epithelioid rhabdomyosarcoma: clinicopathologic analysis of 16 cases of a morphologically distinct variant of rhabdomyosarcoma. 2192 82


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