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)

The local and systemic invasiveness of soft-tissue sarcomas may depend upon an interaction between the primary tumour and the extracellular matrix in which the proteolytic enzyme, urokinase plasminogen activator (uPA), may have an important role. We analyzed the expression of uPA in soft-tissue sarcoma using a luminescent immunoassay technique, and examined the relationships between different uPA levels and tumour characteristics and behaviour. We evaluated 69 adult patients with surgically treated soft-tissue sarcomas (MFH 43, leiomyosarcoma 8, liposarcoma 5, synovial sarcoma 4, others 9) of the extremities and trunk wall. Sixteen developed local recurrences, 26 developed metastases, and 5 had both. The median follow-up for survivors was 55 (30-80) months. The median uPA level was 1.4 (0.04-10.6) ng/mg protein. Increasing uPA levels correlated with increasing grade, malignant fibrous histiocytomas, leiomyosarcomas, DNA non-diploidy, tumour necrosis, local recurrence, and metastasis. Storiform-pleomorphic MFH had higher uPA levels than the myxoid variant. A cut-off value of 0.25 ng/mg protein was identified, above which local recurrence and metastasis occurred more frequently. High uPA levels appear to reflect the malignant phenotype in soft-tissue sarcoma, thus supporting the role of uPA as a prognostic indicator.
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PMID:Urokinase-plasminogen-activator levels and prognosis in 69 soft-tissue sarcomas. 879 66

Thirteen fine-needle aspiration specimens from 10 patients with histologically proven synovial sarcoma are described. The aspiration biopsy specimens were obtained from the primary tumor in five cases, locally recurrent tumors in four cases, pulmonary metastases in three cases, and mediastinal metastasis in one case. Patient's ages ranged from 22 years to 65 years; there were four women and six men. All cases had a confirmation biopsy and/or resection specimen that were reviewed. Histologic subtypes included monophasic fibrous (5 cases), monophasic epithelial (1 case), biphasic (3 cases), and poorly differentiated (1 case). The majority of the aspiration biopsy specimens were similar with moderate to marked smear cellularity dominated by cohesive clusters of spindle-shaped cells with ovoid, hyperchromatic nuclei and scanty tapering cytoplasm. Nucleoli were not prominent. Epithelial tumor cells with ovoid to round, mostly regular, centrally to eccentrically located nuclei, surrounded by scant to abundant cytoplasm predominated in one case (monophasic epithelial) and were admixed with spindle cells in a second (classical biphasic). Multi-nucleated tumor giant cells were not observed in any of the tumors. In biphasic synovial sarcoma, the neoplastic spindle cells are generally more numerous and frequent than the epithelial cells, making distinction from monophasic synovial sarcoma or other spindle cell soft tissue tumors difficult. Although synovial sarcoma may be diagnosed by fine-needle aspiration cytology, clinical correlation, especially in monophasic types, is necessary to minimize errors in sarcoma classification.
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PMID:Fine-needle aspiration biopsy of synovial sarcoma. A cytomorphologic analysis of primary, recurrent, and metastatic tumors. 898 Mar 53

Soft-tissue sarcomas (STS) of the extremities are characterized by a high rate of local recurrences. Limb salvage approaches using multimodality therapy protocols have replaced amputation. In order to evaluate isolated hyperthermic limb perfusion (ILP) in a multimodality therapy concept, we reviewed our patients treated using this method. Between January 1982 and December 1995, 25 ILPs, using cisplatin, melphalan and adriamycin, were performed in 22 patients with STS. Forty percent were treated for local recurrences; histology was dominated by malignant fibrous histiocytoma (MFH) and synovial sarcoma. In all, 68% of the STS were classified as UICC stage IIb or IIIa/b. Most of the cases (14) underwent wide or radical resection, 4 patients received intraoperative radiotherapy, and 5 were treated with external beam radiation. Complications were recorded in 32% of the cases. With a median follow-up of 45 months (range 1-143), the 5-year overall survival rate was 81%. The median recurrence-free time was 19 months and the 5-year disease-free survival rate 34%. There were 13 local failures, and distant metastases developed in 36% of the patients. Concerning high-grade sarcomas (UICC stage IIb, IIIa/b), we found local recurrences in 75% of all cases. Five of 11 patients with local failures underwent perfusion after they refused amputation, and 7 incompletely resected STS received ILP without reoperation. All of these demonstrated local recurrence. This rate of local recurrence proved to be different from patients with tumor-free resection margins (p = 0.0001, log-rank test). The amputation rate after isolated limb perfusion was 27% (mean 11 months after treatment). Long-term results of ILP showed a considerable local recurrence rate and a low disease-free survival. Perfusion in patients without tumor-free resection margins does not prevent local recurrence. We conclude that ILP with cisplatin, melphalan and adriamycin should be considered carefully and is not an additional treatment strategy of fist choice.
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PMID:[Results of isolated hyperthermic extremity perfusion in soft tissue sarcomas within the scope of a multimodality treatment concept]. 932 49

Our purpose was to study the role of the expression of P-glycoprotein (Pgp) and glutathione S transferase-pi (GST-pi) in predicting the response to chemotherapy, relapse-free interval, and survival of patients with synovial sarcoma (SS). Thirty-seven cases of primary SS, without regional lymph node or distant metastases, were studied. There were 17 females and 20 males, ranging in age from 7 to 81 years (median, 31 years) with tumors located in the lower extremity (n = 24) upper extremity (n = 5) and trunchus (n = 8). The cases were retrospectively studied without knowledge of clinical course to compare the immunohistochemical expression of Pgp and GST-pi, flow cytometry parameters (ploidy and % of cells in S+G2 phases), and PCNA and Ki-67 labeling of primary tumors before any therapy, with that observed in local recurrences and metastases after chemotherapy. The relationship of the aforementioned parameters with clinicopathological features (gender, age, and histo-blood group of the patients, size, location, histological subtype. TNM stage, and clinical response to chemotherapy of the tumors) was also evaluated. Results revealed that Pgp and GST-pi were expressed in 29.7% and 40.5% of the cases, respectively. In 48.6% of the tumors there was expression of a least one of the drug resistance markers. The markers were coexpressed in 25.0% of the tumors. The prevalence of Pgp expression was lower, but not significantly, in stage I-II (17.6%) than in stage III (40.0%) tumors, and also in cases without clinical progression (16.7%), than in cases with (36.0%). No such differences were observed for GST-pi expression. Pgp and GST-pi expressions were significantly associated with biphasic SS and were particularly noticeable in solid/glandular areas of biphasic SS. The expression of the drug resistance markers was not significantly associated with gender, age, and histo-blood group of the patients, dimension, location, and proliferative activity of the tumors; it was also not significantly related to relapse-free interval and survival of the patients. The expression of Pgp and GST-pi was not significantly associated either to response to chemotherapy or influenced by chemotherapy. We conclude that Pgp and GST-pi expressions are not good predictors response to of the chemotherapy in patients with localized SS. Other drug resistance mechanisms may be active in SS.
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PMID:Synovial sarcoma: immunohistochemical expression of P-glycoprotein and glutathione S transferase-pi and clinical drug resistance. 911 70

Soft tissue sarcomas (STS) arising in the foot are rare in children. From 1975 to 1994, 18 children (median age, 13.5 years) were treated at St Jude Children's Research Hospital for STS of the foot. Five children had rhabdomyosarcoma (RMS), with alveolar histology in four cases. All of these patients presented with metastatic disease, which proved fatal within 9 to 24 months despite combined modality treatment with chemotherapy, radiation, and surgery. Thirteen patients had nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The most common histological variant was synovial sarcoma (7 patients). Of the 10 who presented with localized disease, seven survived 1 to 12 years (median, 7 years). Surgical treatment for these consisted of local excision (n = 2), wide local excision (n = 3), below knee amputation (n = 1 ), ray amputation (n = 1). Three received supplemental radiation, and one was also treated with chemotherapy. Local or distant recurrence proved fatal in the three other children who had localized disease. Three children who presented with metastatic NRSTS died 8 to 14 months after diagnosis. All surviving patients are without significant functional disability. In our experience, pediatric RMS of the foot has a poor outcome, attributable to both alveolar histology and presence of metastatic disease at diagnosis. In contrast, NRSTS of the foot is more often localized, and limited surgery with adjuvant radiation in the absence of clear margins should be the treatment of choice.
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PMID:Outcome of treatment for pediatric sarcoma of the foot: a retrospective review over a 20-year period. 926 66

High-grade sarcomas have a high rate of local recurrence as well as distant metastases. This has led to the development of intra-arterial chemotherapy (IAC) as part of a multimodal approach to control local disease and/or reduce the extent of surgical resection. Intra-arterial catheters are positioned by an interventional radiologist into the feeding vessels of the tumor. Adriamycin and 5-fluorodeoxyuridine are infused intra-arterially. Cisplatinum, with or without granulocyte colony stimulating factor, is given systemically. Patients usually experience acute self-limited soft-tissue inflammation in the treated area. In our experience of 118 patients, 3 patients experienced soft-tissue necrosis that required excision and reconstruction. The first was treated for synovial sarcoma of a metatarsal. After IAC with Adriamycin, she sloughed the skin, subcutaneous tissue, and some of the posterior compartment musculature of her calf. This tissue was debrided. A gastrocnemius flap and skin graft were used for coverage. She is free of disease and ambulatory. The second patient was treated with IAC Adriamycin for a radial head chondrosarcoma. She developed soft-tissue slough, which became infected with Pseudomonas. She required extensive debridement of the skin, subcutaneous tissue, and muscle, and was subsequently reconstructed with a latissimus flap and a split-thickness skin graft (STSG). She later developed a local recurrence requiring amputation. The latissimus was elevated and used to cover the distal stump. She also is free of disease. The third patient was treated with IAC Adriamycin for Ewing's sarcoma of the right femur. This was complicated by fat necrosis and persistent pain. Subsequent radiotherapy only worsened her symptoms. She underwent wide excision and muscle flap/STSG repair, which relieved her pain. She is currently ambulatory and free of disease. In conclusion, as the use of IAC continues, its complications may become more common. Our experience with this previously unknown entity is illustrated and therapeutic options are discussed.
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PMID:Soft-tissue complications of intra-arterial chemotherapy for extremity sarcomas. 955 93

Controversy still exists regarding the validity of parameters commonly used in the evaluation of prognosis of patients with synovial sarcoma (SS). Forty-nine cases of previously untreated primary SS (23 females and 26 males, ranging in age from 7 to 81, with 31 tumors located in the lower extremity, 8 at the upper extremity and 10 at the trunchus), without regional lymph-node or distant metastases were studied. We investigated the relationship between (flow and image) DNA cytometry, proliferation activity, clinicopathologic parameters, and relapse-free and overall survival of the patients. The prognostic value of gender, age, duration of symptoms, location, compartmentalization, size, adequacy of surgical margins, residual tumor, adjuvant therapy, histologic subtype, extent of necrosis, glandular differentiation, calcification, and extent of hemangiopericytic areas, mitotic rate, amount of mast cells, blood vessel invasion, histologic (UICC and NCI) grades, DNA ploidy, percentage of cells in S and S+G2 phases, PCNA and Ki-67 labeling indices (LI), and TNM (UICC) stage of the tumors, were evaluated by univariate and multivariate (Cox hazard model) analyses. Short duration of symptoms (<12 months), biphasic SS, scarcity of mast cells (<10/10 HPF), high mitotic rate (> or =10/10 HPF), high histologic grade (grade 3), high PCNA-LI (> or =20%), high Ki-67-LI (> or =10%), DNA aneuploidy, and advanced TNM stage (stage III) were features associated with significantly shorter relapse-free and overall 5-year survival rates in the univariate analyses. Scarcity of mast cells, high mitotic rate, or high PCNA-LI were significant predictors of poor survival, in addition to TNM stage in the multivariate analyses. The amount of mast cells was inversely correlated with mitotic rate and PCNA-LI. Scarcity of mast cells, high mitotic rate, or high PCNA-LI are factors associated with poor prognosis, in addition to advanced TNM stage in patients with localized SS.
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PMID:Synovial sarcoma. Evaluation of prognosis with emphasis on the study of DNA ploidy and proliferation (PCNA and Ki-67) markers. 958 99

The extracellular matrix (ECM) forms a framework for cell adhesion, but it also regulates growth and differentiation. Normal and malignant cells interact with the ECM via specific receptors, the integrins. To explore the mechanisms of growth and spread in soft tissue sarcomas the expression of the major ECM molecules and their corresponding integrin receptors were studied by immunohistochemistry in high-grade soft tissue sarcomas: malignant fibrous histiocytoma (20 cases), malignant peripheral nerve sheath tumour (17 cases) and synovial sarcoma (21 cases). The expression pattern was compared with cell proliferation and clinical outcome. Integrins were found to be expressed according to histological pattern. In synovial sarcomas, the epithelial component showed a high alpha 2 but negative or minimal detection of alpha 5 expression, while a weak alpha 2 expression and a moderate alpha 5 expression were found in the spindle cell component. No alpha 2 expression was detected in malignant fibrous histiocytoma, and minimal alpha 5 expression was detected in malignant schwannoma. The alpha 6 expression levels were positively correlated with the occurrence of metastases in all types of sarcomas studied. The expression of ECM molecules was downregulated and irregular in most tumours. In conclusion, the divergent integrin expression pattern could be useful in the diagnosis and classification of soft tissue sarcomas. Furthermore, since high laminin receptor expression correlates with occurrence of metastases, it could become a useful prognostic marker.
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PMID:Adhesion molecules in high-grade soft tissue sarcomas: correlation to clinical outcome. 971 99

The role and value of chemotherapy for soft tissue sarcomas remain unclear. Seventeen patients with pulmonary metastatic soft tissue sarcomas underwent treatment with chemotherapy, and the clinical efficacy and prognosis were studied. Six patients with synovial sarcomas, 4 with malignant fibrous histiocytomas, 4 with neurosarcomas, and the remaining 3 patients with leiomyosarcoma, extraskeletal osteosarcoma, and extraskeletal chondrosarcoma, were studied. Cases with small round cell sarcomas were excluded. The chemotherapy agents were ifosfamide in 10 cases, combination of ifosfamide and adriamycin in 5 cases, or cisplatin and adriamycin in 2 cases. Of the 17 patients, seven had partial responses radiographically and five had pulmonary metastases from synovial sarcoma. Eight patients underwent resection of pulmonary metastases following chemotherapy, and they were found to be residual tumor cells histologically. Twelve of the patients died of disease at 6-108 months (median, 30 months) from the time of the initial therapy, and five patients have survived from 1-53 months (median, 30 months). The absolute three-year survival rate, according to the Kaplan-Meier method, for all 17 patients was 39%. In the two cases with no change and progressive disease, all patients were dead within 2 years, while in the seven partial response cases, two patients were dead, four were alive with pulmonary metastases, and only one case was disease-free at this writing. The survival rate for patients with partial response was significantly higher than for patients with no response. Although the cure rate of pulmonary metastatic soft tissue sarcomas is still low, the combination of chemotherapy and surgery has been shown to result in prolonged survival.
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PMID:[Chemotherapy for pulmonary metastases of soft tissue sarcoma]. 975 95

The use of fine-needle aspiration biopsy (FNAB) in the initial evaluation of pediatric bone and soft tissue tumors is controversial, especially for those patients being considered for histiogenetic-specific therapeutic protocols, e.g., the Intergroup Rhabdomyosarcoma Study Group, the Pediatric Oncology Group. We retrospectively reviewed 33 consecutive FNAB specimens (28 primary tumors, 5 metastases) from 32 pediatric patients (< or = 19 yr of age), none of whom had a previously established tumor diagnosis. In one patient, FNAB of the primary tumor and a presumed axillary metastasis were obtained concomitantly. The cytomorphologic analysis included osteosarcoma, eight patients; rhabdomyosarcoma, five; neuroblastoma, five; Ewing's sarcoma/primitive neuroectodermal tumor, four; Langerhans' cell histiocytosis, three; and one each synovial sarcoma, undifferentiated sarcoma, infantile myofibromatosis, fibroma, chondroblastoma, chondromyxoid fibroma, and desmoplastic small round-cell tumor. Ancillary studies, e.g., immunocytochemical analysis, were used in 13 cases. Cytogenetic analysis helped to confirm one Ewing's sarcoma [t (11;22) (q24;q12)] and one synovial sarcoma [t(X;18) (p11;q11)]. With adequate FNAB specimens, a histogenetic-specific diagnosis was rendered in 27 (93%) of 29 cases, and all were correctly recognized as either benign or malignant. One case each of Langerhans' cell histiocytosis, chondroblastoma, and infantile myofibromatosis yielded unsatisfactory specimens. Fibroma and desmoplastic small round-cell tumor were initially misclassified as nodular fasciitis and rhabdomyosarcoma, respectively. Of 18 patients clinically eligible for histogenetic-specific therapy protocols, an accurate diagnosis was obtained in 17 patients. With a multidisciplinary approach and judicious use of ancillary studies, FNAB represents a highly accurate and cost-effective technique for the diagnosis of pediatric bone and soft tissue tumors, especially sarcomas, and should be considered as a viable diagnostic technique for pediatric therapeutic protocols.
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PMID:The role of fine-needle aspiration biopsy in the initial diagnosis of pediatric bone and soft tissue tumors: an institutional experience. 979 16


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