Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews the clinicopathologic features and the biological behavior of 24 cases of synovial sarcoma that took origin from the cervical prevertebral connective tissue space and manifested as a retropharyngeal tumor or as a palpable mass in the anterior or posterior cervical triangle. The age of the 24 patients ranged from 10 to 51 years, with a median of 19 years. Ten patients were women and 14 men. Hoarseness or difficulty in breathing or swallowing were the first symptoms in eight patients. The tumors were solitary and ranged from 2 to 10 cm in greatest dimension. Microscopically, all of the cases showed the characteristic biphasic cellular pattern of a synovial sarcoma, with epithelioid and fibrosarcoma-like areas in varying proportions. Synovioblastic origin of the neoplasm was confirmed by the results of histochemical staining procedures and, in 1 case, by the examination with the electron microscope. Of the 21 cases followup information, 12 had died (10 with pulmonary metastasis) and 9 were alive and free of symptoms. Prompt and complete surgical removal is required to prevent complications from recurrent tumor growth or metastasis.
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PMID:Synovial sarcoma of the neck: a followup study of 24 cases. 16 80

We carried out DNA cytofluorometry with propidium iodide stain on the 17 cases of soft tissue tumors including giant cell tumor of the tendon sheath, pigmented villonodular synovitis, 2 hemangiomas, 3 lipomas, 5 schwannomas, 3 neurofibromas, liposarcoma and synovial sarcoma. The benign tumors were characterized by regular polyploidization with very few S-phase cells, indicating slow tumor growth. Most of the malignant soft tissue tumors were associated with remarkable polyploidization with an increase in S-phase cells. However, some malignant tumors did not show polyploidization. We concluded, therefore, that an increase in S-phase cells is an important, cytofluorometric criterion for malignancy of soft tissue tumors.
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PMID:[DNA cytofluorometry of soft tissue tumors]. 609 47

We have recently demonstrated that a single local injection of the avian pathogen Newcastle disease virus (NDV; strain 73-T) causes complete regression of human neuroblastoma xenografts in athymic mice (R. M. Lorence, K. W. Reichard, B. B. Katubig, H. M. Reyes, A. Phuangsab, B. R. Mitchell, C. J. Cascino, R. J. Walter, and M. E. Peeples. J. Natl. Cancer Inst., 86: 1228-1233, 1994). In this report, we tried to determine if this in vivo antineoplastic effect of NDV extends to human sarcomas. Athymic mice with s.c. HT1080 fibrosarcoma xenografts (7-14 mm) were randomly divided into two groups and treated i.t. with a single injection of either 10(7) plaque-forming units of NDV or phosphate-buffered saline. Complete tumor regression occurred in 8 of 10 mice treated with NDV while unabated tumor growth occurred in all 9 mice treated with phosphate-buffered saline (P < 0.001). To determine if complete tumor regression was long lasting, the 8 mice were monitored for 1 year, during which time no tumor recurred. To test the antitumor effects of NDV on tumors derived from a fresh human sarcoma, a similar experiment was performed in athymic mice using TH15145 synovial sarcoma xenografts at their first and second passages. Of 9 mice with TH15145 xenografts, a single i.t. injection of NDV (10(7) plaque-forming units) caused complete regression of 3 tumors and > 80% regression in 3 more tumors. In contrast, tumors in all 5 mice treated with phosphate-buffered saline exhibited unabated growth (P < 0.03 for > 80% tumor regression). Since HT1080 fibrosarcoma cells express the N-ras oncogene, we explored the effects that transfection of this oncogene has on the sensitivity to NDV. Cultured human fibroblasts that were made tumorigenic following N-ras-transfection were found to be 1000-fold more sensitive to NDV than normal fibroblasts in a cytotoxicity assay. Oncogene expression by the HT1080 fibrosarcoma may therefore contribute to the long-lasting complete regression of this sarcoma following a single local injection of NDV.
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PMID:Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. 795 37

Local recurrence of tumor is a common phenomenon in soft tissue sarcoma (STS) and may be accompanied by an increase in malignant potential. In the present study, an increase of proliferative activity in recurrent tumors compared to primary tumors was observed using a silver stain for nucleolar organizer regions (AgNOR), and its implication for predicting prognosis is assessed. 44 patients with STS showing local tumor recurrence were selected. Local recurrence was defined as new tumor growth more than 2 months after the initial surgery in the same region where the primary tumor occurred. All patients received surgery, followed in 11 patients by adjuvant radiotherapy and/or chemotherapy. The histologic subtype was malignant fibrous histiocytoma in 22 cases, synovial sarcoma in 5, leiomyosarcoma in 4, liposarcoma in 3, malignant schwannoma in 3, and others in 7. The interval between initial surgery and local recurrence ranged from 2 to 72 months. No patients changed from one histological subtype to another. Histological changes included an increase in mitosis, cellularity, and sclerosis in 43.2, 31.8, and 27.3%, respectively. The AgNOR count (mean +/- SD) in recurrent tumors (7.22 +/- 2.59) was significantly higher than that in primary tumors (5.58 +/- 2.28; p < 0.0057), clearly showing a tendency for an increase in proliferative activity during recurrence. The 5-year survival rate of patients with a marked increase (> 4) in AgNOR count (16.7%) was worse than with minor to moderate increases (60.0%; p < 0.02). Marked AgNOR increase was more frequently observed in the tumors located in the head and neck and retroperitoneum (40%) than in other sites (9%). Irrespective of the primary site of tumors, a marked AgNOR increase resulted in an unfavorable prognosis. Multivariate analysis of change in histologic factors including AgNOR, cellularity, mitotic counts, pleomorphism, myxoid change, necrosis, sclerosis, and tumor size showed that increase of AgNOR counts was significant (p < 0.05). The present findings suggest that AgNOR counts can be used as a prognostic factor in recurrent STS.
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PMID:Usefulness of argyrophilic nucleolar organizer staining for predicting prognosis of patients with recurrent soft tissue sarcoma. 819 7

Although soft tissue sarcoma has a high incidence of p53 mutations, it is not clear if such alterations facilitate tumor growth and metastasis. In this study, fresh autologous normal lymphocytes, normal muscle, primary and metastatic sarcoma tissues from a single synovial sarcoma patient were examined for p53-related alterations that potentially associated with sarcoma tumor development and metastasis. Normal tissues contain two wild-type p53 alleles. Primary sarcoma had one chromosome 17p p53 allelic deletion without apparent p53 mutation in the other allele. However, metastatic tumor had deletion of one p53 allele with an exon 5 codon 135 missense mutation in the other allele. This p53 gene point mutation in the metastasis was associated with the production of mutated p53 protein. A small clone of cells harboring the identical p53 gene point mutation was identified in the primary tumor using mutant allele specific PCR amplification, albeit at levels much less than in the metastatic sarcoma. This single patient example indicate that soft tissue sarcoma metastasis can develop from clonal expansion of primary tumor cells bearing p53 mutations.
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PMID:Soft tissue sarcoma metastasis from clonal expansion of p53 mutated tumor cells. 864 65

Genome-wide expression profiling revealed overexpression of the gene encoding frizzled homologue 10 (FZD 10), a cell-surface receptor for molecules in the Wnt pathway, as a potential contributor to synovial sarcomas (SS). Northern blotting and immunohistochemical staining confirmed that expression levels of FZD 10 were very high in nearly all SS tumors and cell lines examined but absent in most normal organs or in some cancers arising in other tissues. Treatment of human SS cells with small-interfering RNA (siRNA) to FZD 10 decreased the amount of its product and suppressed growth of SS cells. Moreover, a polyclonal antibody specifically recognizing the extracellular domain (ECD) of FZD 10 was markedly effective in mediating ADCC against FZD 10-overexpressing synovial sarcoma cells in vitro. Injection of the antibody into SS xenografts in nude mice attenuated tumor growth, and TUNEL assays revealed clusters of apoptotic cells in antibody-treated xenografts. Taken together, these findings suggest that a humanized antibody against FZD 10 might be a promising treatment for patients with tumors that overexpress FZD 10; minimal or no adverse reactions would be expected because FZD 10 protein is not abundant in vital organs.
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PMID:Therapeutic potential of antibodies against FZD 10, a cell-surface protein, for synovial sarcomas. 1600 99

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and tumor growth and progression. The overexpression of HIF-1alpha protein has been reported to be associated with a worse prognosis in various cancers. However, the expression of HIF-1alpha in soft-tissue sarcomas has not yet been characterized. The expression of HIF-1alpha protein was immunohistochemically determined in 49 specimens of soft-tissue sarcomas including malignant fibrous histiocytoma (29 patients), synovial sarcoma (12 patients), leiomyosarcoma (four patients), and malignant peripheral nerve sheath tumors (four patients). The 49 samples consisted of 40 primary lesions and nine local recurrences. An immunohistochemical analysis showed the nuclear accumulation of HIF-1alpha protein in 35 (71.4%) samples. The expression of HIF-1alpha was negative in 14 (28.6%) cases, weak in nine (18.4%), moderate in 17 (35.4%), and strong in nine (18.4%). The patients with a strong or moderate expression of HIF-1alpha had a significantly shorter overall survival rate in comparison with those with a weak or negative expression in a univariate analysis (P = 0.029; log-rank test) and multivariate analysis (P = 0.018). This is the first report that demonstrated an overexpression of HIF-1alpha protein to be an independent prognostic factor for soft-tissue sarcomas.
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PMID:Expression of hypoxia-inducible factor (HIF)-1alpha as a biomarker of outcome in soft-tissue sarcomas. 1710 26

Mutations of the p53 gene are uncommon in synovial sarcoma, a high-grade tumor genetically characterized by the chromosomal translocation t:(X;18), which results in the fusion of SS18 with members of SSX gene family. Although implicated in tumorigenesis, the mechanisms by which SS18-SSX promotes tumor growth and cell survival are poorly defined. Here, we show that SS18-SSX1 negatively regulates the stability of the tumor suppressor p53 under basal conditions. Overexpression of SS18-SSX1 enhanced p53 ubiquitination and degradation in a manner dependent on the ubiquitin ligase activity of HDM2. The negative effect of SS18-SSX1 expression on p53 was mediated by its ability to promote HDM2 stabilization through inhibition of HDM2 autoubiquitination. Furthermore, SS18-SSX1 expression altered the induction of p53-regulated genes in response to cellular stress by abrogating the transactivation of HDM2, PUMA, and NOXA but not p21. Our data uncover a novel mechanism whereby SS18-SSX1 can negatively regulate p53 tumor-suppressive function by increasing the stability of its negative regulator HDM2 and suggest that chemical compounds that target the p53-HDM2 regulatory axis may be of therapeutic benefit for the treatment of synovial sarcoma.
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PMID:The oncoprotein SS18-SSX1 promotes p53 ubiquitination and degradation by enhancing HDM2 stability. 1823 68

We previously reported Frizzled homolog 10 (FZD10), a member of the Frizzled family, to be a promising therapeutic target for synovial sarcomas. In this report, we established a murine monoclonal antibody (MAb), namely, MAb 92-13 that had specific binding activity against native FZD10 product expressed in synovial sarcoma cell lines. Subsequent immunohistochemical analyses with the MAb 92-13 confirmed an absence or hardly detectable level of FZD10 protein in any normal human organs. We confirmed the specific binding activity of this MAb in vivo after injection of fluorescent-labeled MAb i.p. or i.v. into the mice carrying synovial sarcoma xenografts by the use of the in vivo fluorescent imaging system as well as radioisotopes. Moreover, MAb 92-13 was effectively internalized into the synovial sarcoma cells after its binding to FZD10 on the cell surface. A single i.v. injection of the Yttrium-90 ((90)Y)-MAb 92-13 drastically suppressed tumor growth of synovial sarcoma in mice without any severe toxicity. Median time to tumor progression was 58 days for mice treated with (90)Y-MAb 92-13 and 9 days for mice treated with non-labeled antibody control or untreated mice (difference = 49 days; P = 7 x 10(-5)). This result indicates that MAb 92-13 could be utilized as the novel treatment modality for synovial sarcoma and other FZD10-positive tumors.
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PMID:Radioimmunotherapy of human synovial sarcoma using a monoclonal antibody against FZD10. 1827 42

The heterogeneity that soft tissue sarcomas (STS) exhibit in their clinical behavior, even within histological subtypes, complicates patient care. Histological appearance is determined by gene expression. Morphologic features are generally good predictors of biologic behavior, however, metastatic propensity, tumor growth, and response to chemotherapy may be determined by gene expression patterns that do not correlate well with morphology. One approach to identify heterogeneity is to search for genetic markers that correlate with differences in tumor behavior. Alternatively, subsets may be identified based on gene expression patterns alone, independent of knowledge of clinical outcome. We have reported gene expression patterns that distinguish two subgroups of clear cell renal carcinoma (ccRCC), and other gene expression patterns that distinguish heterogeneity of serous ovarian carcinoma (OVCA) and aggressive fibromatosis (AF). In this study, gene expression in 53 samples of STS and AF [including 16 malignant fibrous histiocytoma (MFH), 9 leiomyosarcoma, 12 liposarcoma, 4 synovial sarcoma, and 12 samples of AF] was determined at Gene Logic Inc. (Gaithersburg, MD) using Affymetrix GeneChip U_133 arrays containing approximately 40,000 genes/ESTs. Gene expression analysis was performed with the Gene Logic Genesis Enterprise System Software and Expressionist software. Hierarchical clustering of the STS using our three previously reported gene sets, each generated subgroups within the STS that for some subtypes correlated with histology, and also suggested the existence of subsets of MFH. All three gene sets also recognized the same two subsets of the fibromatosis samples that we had found in our earlier study of AF. These results suggest that these subgroups may have biological significance, and that these gene sets may be useful for sub-classification of STS. In addition, several genes that are targets of some anti-tumor drugs were found to be differentially expressed in particular subsets of STS.
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PMID:Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors. 1846 Feb 15


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