Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soft tissue sarcomas are rare and may be a source of problems for diagnosis and treatment. Four types of genetic disorders can be distinguished: translocations, gene amplifications, mutations and complex genetic imbalances. Detection of these disorders may help in diagnosis and in determining prognosis. Detection of specific translocation is recommended in synovial sarcoma, alveolar rhabdomyosarcoma or PNET diagnosis because of therapeutic consequences; in case of rarer histologic type (low grade fibromyxoid sarcoma, clear cell sarcoma, infantile fibrosarcoma...), it may confirm the diagnosis. In some cases, some translocations have a prognostic value (alveolar rhabdomyosarcoma) whereas it is discussed in others (synovial sarcoma). The techniques used to detect these translocations are very sensitive so it may be used to detect microscopical metastasis (bone marrow metastasis of alveolar rhabdomyosarcoma for example). Detection of MDM2 and CDK4 genes amplifications (FISH or quantitative PCR) may be sometimes useful in well differentiated and dedifferentiated liposarcomas diagnosis. Mutation detection of KIT or PDGFRA may help in GIST diagnosis and type of mutation is predictive of response to treatment. Study of complex genomic imbalances in sarcomas is not used in routine practice but remains useful in research.
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PMID:[Soft tissue sarcomas: update on molecular data]. 1644 27

Soft-tissue sarcomas spread predominantly to the lung and it is unclear how often FDG-PET scans will detect metastases not already obvious by chest CT scan or clinical examination. Adult limb and body wall soft-tissue sarcoma cases were identified retrospectively. Ewing's sarcoma, rhabdomyosarcoma, GIST, desmoid tumors, visceral tumors, bone tumors, and retroperitoneal sarcomas were excluded as were patients imaged for followup, response assessment, or recurrence. All patients had a diagnostic chest CT scan. 109 patients met these criteria, 87% of which had intermediate or high-grade tumors. The most common pathological diagnoses were leiomyosarcoma (17%), liposarcoma (17%), and undifferentiated or pleomorphic sarcoma (16%). 98% of previously unresected primary tumors were FDG avid. PET scans were negative for distant disease in 91/109 cases. The negative predictive value was 89%. Fourteen PET scans were positive. Of these, 6 patients were already known to have metastases, 3 were false positives, and 5 represented new findings of metastasis (positive predictive value 79%). In total, 5 patients were upstaged by FDG-PET (4.5%). Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging as part of the initial staging of soft-tissue sarcomas was unlikely to alter management in our series.
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PMID:FDG PET/CT in Initial Staging of Adult Soft-Tissue Sarcoma. 2325 Oct 96

Sarcomas collectively represent over 100 different subtypes of bone and soft tissue tumors of mesenchymal origin. The low response rate to cytotoxic chemotherapies has necessitated the need for development of either histologically driven or pathway-specific targeted therapies. As our understanding of the molecular mechanisms driving certain subtypes is rapidly advancing, the number of targeted therapies is also increasing. Recently identified novel druggable targets include the MDM2 amplifications in well-differentiated and dedifferentiated liposarcomas, the new translocation NAB2:STAT6 of solitary fibrous tumors, the angiopoeitin-TIE2 pathway in angiosarcoma, the suppression of Mcl1 in X:18/synovial sarcomas, the mTOR pathway in malignant peripheral nerve sheath tumors, CDK4 in alveolar rhabdomyosarcoma, cMET regulation in alveolar soft parts sarcoma, the metabolic abnormalities in wild-type/SHD GIST, and the lack of argininosuccinate synthetase 1 expression seen in most sarcomas. It is through a fundamental understanding of sarcoma biology that clinical trials based on molecular targets can be developed.
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PMID:Novel pathways and molecular targets for the treatment of sarcoma. 2366 Dec 64

The aim of the present study was to explore ERG immunoreactivity in a series of sarcomas, GIST and malignant rhabdoid tumor (MRT), considering the not fully elucidated specificity and sensitivity of this antibody. Paraffin-embedded tissue microarrays from those tumors were stained with anti-ERG against the C-terminus [(EPR3864(2)] and N-terminus (Clone 9FY). EPR3864(2) was positive in almost all angiosarcomas, and MRT.GIST were positive in a large proportion of cases (38.4%), and more than half the synovial sarcomas (52.7%) revealed EPR3864(2) staining. Several chondrosarcomas, osteosarcomas, rhabdomyosarcoma and Ewing's sarcoma family of tumors (ESFT) presented EPR3864(2) expression in a lower number of cases. 9FY was positive in most of the angiosarcomas; however, only sporadic ESFT and synovial sarcoma were positive and the other tumors tested were negative. Fourteen ESFT with EWSR1/Fli-1 gene fusion presented positive nuclear staining for EPR3864(2). Similarly, 5 ESFT with EWSR1/Fli-1 gene fusion presented positive staining for 9FY. We must stress that the difference between the present and previous studies may be due to the source of the anti-ERG employed, anti-ERG against C or N-terminus, protein cross-reactivity and dilution. In conclusion, specificity for ERG staining in sarcomas should be considered with caution and the immunoexpression is undoubtedly influenced by clone and antibody selection.
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PMID:Immunoreactivity using anti-ERG monoclonal antibodies in sarcomas is influenced by clone selection. 2490 28

Peritoneal tumour dissemination represents an advanced tumour stage and survival rates are usually low. In the past, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established in adults leading to increased survival rates in comparison to chemotherapy alone. CRS and HIPEC are indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei, and in peritoneal metastases from gastrointestinal and ovarian cancers in adults. The incidence of peritoneal surface malignancies in children seems to be lower than in adults, but the incidence is unknown. Nevertheless, peritoneal carcinomatosis/sarcomatosis may occur in patients suffering from desmoplastic small round cell tumour (DSRCT), soft tissue sarcoma (rhabdomyosarcoma, leiomyosarcoma, GIST or liposarcoma), as well as in patients with gastrointestinal cancers. CRS and HIPEC have been established as a novel treatment option in children suffering from peritoneal carcinomatosis/sarcomatosis in very few centres worldwide. This paper reviews the indications, treatment regimens, and pitfalls of this approach in children.
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PMID:[Cytoreductive surgery and HIPEC for peritoneal malignancies in children]. 2553 34

Selective tyrosine kinase inhibitor (TKI) targeting KIT and PDGFRA is the frontline therapy for metastatic and unresectable GIST patients. Some initially responsive patients experience tumor progress because of secondary drug resistance, and some cases can develop heterogeneous differentiation. Here we report a rare case of recurrent retroperitoneal extra-GIST with rhabdomyosarcomatous and chondrosarcomatous differentiation with TKI therapy after surgical tumorectomy. Histology, immunohistochemistry, and mutational analysis were performed on primary and recurrent samples. The current case represents the first report of a recurrent retroperitoneal extra-GIST harboring mixed morphologic phenotypes of rhabdomyosarcoma and chondrosarsoma after TKI treatment. The dual differentiation can represent diagnostic pitfall.
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PMID:Recurrent retroperitoneal extra-GIST with rhabdomyosarcomatous and chondrosarcomatous differentiations: a rare case and literature review. 2646 33

Microtubules are known to be one of the most attractive and validated targets in cancer therapy. However, the clinical use of drugs that affect the dynamic state of microtubules has been hindered by chemoresistance and toxicity issues. Accordingly, the development of novel agents that target microtubules is needed. Here, we report the identification of novel compounds with pirrole and carboxylate structures: ethyl-2-amino-pyrrole-3-carboxylates (EAPCs) that provide potent cytotoxic activities against multiple soft tissue cancer cell lines in vitro. Using the MTS cell proliferation assay, we assessed the activity of EAPCs on various cancer cell lines including leiomyosarcoma SK-LMS-1, rhabdomyosarcoma RD, gastrointestinal stromal tumor GIST-T1, A-673 Ewing's sarcoma, and U-2 OS osteosarcoma. We found that in the majority of cases, two EAPC compounds (EAPC-20 and EAPC-24) considerably inhibited cancer cell proliferation in vitro. The growth-inhibitory effects of EAPC-20 and EAPC-24 were time and dose dependent. The molecular mechanisms of action of these compounds were because of the inhibition of tubulin polymerization and induction of a robust G2/M cell-cycle arrest, leading to considerable accumulation of tumor cells in the M-phase. Finally, EAPCs induced tumor cell death by apoptotic pathways. The above-mentioned effects were also observed in most soft tissue tumor cell lines and the gastrointestinal stromal tumor cell line investigated. Taken together, our data identify potent antitumor activity of EAPCs in vitro, thus providing a novel scaffold with which to develop potent chemotherapeutic agents for cancer therapy.
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PMID:Ethyl-2-amino-pyrrole-3-carboxylates are novel potent anticancer agents that affect tubulin polymerization, induce G2/M cell-cycle arrest, and effectively inhibit soft tissue cancer cell growth in vitro. 2712 79

Since its foundation by remarkably talented and insightful individuals, prominently including Pepper Dehner, pediatric soft tissue tumor pathology has developed at an immense rate. The morphologic classification of tumoral entities has extensively been corroborated, but has also evolved with refinement or realignment of these classifications, through accruing molecular data, with many derivative ancillary diagnostic assays now already well-established. Tumors of unclear histogenesis, classically morphologically undifferentiated, are prominent amongst pediatric sarcomas, however, the classes of undifferentiated round- or spindle-cell-tumors-not-otherwise-specified are being dismantled gradually with the identification of their molecular underpinnings. Within recent years, for example, numerous subcategories of 'Ewing-like' round cell sarcoma have emerged. Such advances have provided the basis for novel diagnostic and prognostic sub-classifications. Efforts at defining cell- or lineage-of-origin for several tumor types have produced interesting insights especially for rhabdomyosarcoma. The remarkably early onset of pediatric sarcomas defies the theory necessitating stochastic accumulation of several somatic mutations for cancer development and indeed, these tumors may be remarkably genomically stable, often belying their aggressive nature. Much is coming to light recently regarding the role of epigenetic modifications in the evolution of these sarcomas. Indeed the morphologic features of embryonal tumors generally (not just sarcomas) may be highly reminiscent of arrested differentiation, and given the tight epigenetic regulation of cell fate determination and cell identity maintenance, a theory of epigenetically-driven oncogenesis sits easily with these tumors. The age-delimited distinct biologies of 'pediatric' and adult GIST are intriguing, particularly, the SDH-deficient 'pediatric' form, driven by a metabolic defect, but resulting in epigenetic dysregulation with genome-wide DNA methylation changes. There is little doubt that many of the gaps in our understanding of pediatric sarcoma biology will be filled by a deeper appreciation of the role of dysregulated epigenetics including chromatin biology, perhaps best exemplified in malignant rhabdoid tumor. The field of pediatric soft tissue tumor pathology grows ever more interesting. Importantly though, it must be emphasized, that none of this progress could have occurred, or indeed continue, without the initial step of accurate diagnosis, founded solidly on morphology - thank you Pepper for your unparalleled contributions to this field! The opportunity to be your apprentice for five years has been a bigger and more positive influence than words can express.
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PMID:Pediatric soft tissue tumor pathology: A happy morpho-molecular union. 2775

Transducin-like enhancer of split 1 (TLE1) is a transcription factor known for its strong overexpression and immunopositivity in synovial sarcoma. Several studies have revealed that its immunopositivity is not always specific to synovial sarcoma, with several cases showing positivity in peripheral nerve sheath tumors and solitary fibrous tumors. Occasional weak staining for TLE1 has also been described in clear cell sarcoma, high-grade chondrosarcoma, Ewing sarcoma, rhabdomyosarcoma, GIST, myxofibrosarcoma, and leiomyosarcoma. Here we present the first unique case of sclerosing epithelioid fibrosarcoma with strong, diffuse TLE1 positivity, resulting in a new consideration for the differential diagnosis of TLE1 positivity.
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PMID:A rare case of TLE1-positive sclerosing epithelioid fibrosarcoma expanding the differential diagnosis of TLE1-positive tumors: a case report. 3102 Feb 73