UMLS:C1261473 - FACTA Search

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Query: UMLS:C1261473 (sarcoma)
25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

STAT proteins constitute a family of transcription factors whose activation by cytokine and non-cytokine receptors leads to tyrosine phosphorylation, dimerization and translocation from the cytoplasm to the nucleus. In the nucleus they activate the transcription of specific genes by binding to consensus DNA elements. STATs 1 and 3 can be activated by both cytokine and non-cytokine receptors, and bind as homodimers or heterodimers to viral simian sarcoma virus (sis)-inducible elements such as that found in the c-fos promoter. Activation of c-Src and EGF receptor tyrosine kinases is associated with progression of breast cancer. Both these events lead to activation of STAT proteins, Src kinases activate STAT3 dependent transcription in mammary epithelial cells and EGF receptor activation can lead to activation of STATs 1 and 3. STAT3 activation has been demonstrated to have a role in oncogenesis and increasingly, activated STAT proteins are found to be activated in human cancer. In this study we describe detailed immunohistochemical analysis of nuclear and cytoplasmic STATs 1 and 3 expression in primary breast carcinomas and correlate this with EGFR, HER2, p53, ER, PR, p21/waf1, Bcl-XL and Ki-67 expression. We also compared expression between normal and tumor tissue. We report here a highly significant correlation between nuclear STAT3 expression and breast cancers compared to normal tissue. We also report a very strong correlation between nuclear STAT3 and EGFR expression in breast cancers. These data clearly demonstrate a strong association between STAT3 activation and breast tumorigenesis and strengthen the assertion that STAT3 activation may play an important role in the tumorigenic conversion of breast tissue mediated by tyrosine kinase signaling pathways.
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PMID:EGFR dependent expression of STAT3 (but not STAT1) in breast cancer. 1171 84

Myxoid/round cell liposarcomas (MLS/RCLS) are characterized by chromosome translocations that result in formation of FUS-CHOP or EWSR1-CHOP fusion oncogenes. More than 95% of the tumors carry one of these fusion genes. FUS-CHOP transforms 3T3 cells and causes MLS/RCLS-like tumors in transgenic mice. The fusion oncoproteins act as abnormal transcription factors and are believed to induce abnormal expression of growth controlling genes as part of their transforming activities. The aim of this study was to search for recurrent abnormal expression patterns of cell cycle regulating proteins and growth factor receptors. A series of 14 MLS/RCLS, 2 MLS/RCLS derived cell lines and a FUS-CHOP transfected human sarcoma cell line were analyzed using immunohistochemistry, Western blotting, and cDNA microarray based screening. The results revealed a highly abnormal expression pattern of several growth controlling proteins. The G1 cyclins D1 and E and their associated kinases CDK4 and CDK2 were strongly overexpressed in all of the tumors. High expression levels were also found for Cdk4/6 inhibitor P16 and CDK2 inhibitors P27 and P57. The growth factor tyrosine kinase receptors PDGFRB and EGFR were present in most cells of all investigated tumors. We conclude that deregulation of G1 controlling proteins is common in MLS/RCLS and that aberrant expression of these proteins is of importance in the pathogenesis of this tumor type.
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PMID:Abnormal expression of cell cycle regulators in FUS-CHOP carrying liposarcomas. 1549 25

Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells. The beneficial effect of the anti-parkinsonian monoamine oxidase-B inhibitor, R-(-)-deprenyl has been shown in a number of different diseases, such as Parkinson's and Alzheimer's disease, atherosclerosis or tumor formation. The role of the cytoskeleton, the main component of cell adhesion, has been suggested in the development of these diseases. Nevertheless, the effect of the drug on cell adhesion has never been examined. In the present study, the authors studied the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal (PC12, rat phaeochromocytoma) and non-neuronal (NIH3T3, NIH3T3/EGFR, NIH3T3/EGFR-e3B1 mouse embryo fibroblasts, and 5180 mouse sarcoma) cells using cell association assay. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 cells, which contain no monoamine oxidase-B, and we observed the same effect in NIH3T3 cells at concentrations lower than those needed for monoamine oxidase-B inhibition. Interestingly, R-(-)-deprenyl increased cell-cell adhesion of tumor cell lines as well. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. At the same time, the monoamine oxidase-B inactive isomer of the drug, S-(+)-deprenyl had no effect on cell-cell adhesion in PC12 and NIH3T3 cells. In this study, the authors described a new, monoamine oxidase-B independent effect of R-(-)-deprenyl on cell-cell adhesion both in neuronal and non neuronal cells. The authors' results with S-(+)-deprenyl suggest that the sterical structure of the drug is an important factor of the observed effect, which is probably a consequence of an irreversible change in the cells.
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PMID:[Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells]. 1585 24

We present an extensive immunohistochemical analysis of 7 mammary sarcomas that did not fit into any specific soft tissue sarcoma category. Histologically, they were composed of spindle cells with highly pleomorphic nuclei and abundant mitoses. Our immunohistochemical antibody panel included pan-cytokeratin (CK), basal cell type CKs (34betaE12, CK5/6, CK14, CK17) and vimentin antibodies, antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers, as well as antibodies to CD34, desmin, h-caldesmon, steroid receptors (estrogen, progesterone, androgen), and EGFR (Her-1). Whereas CKs, CD34, desmin, and h-caldesmon were not expressed, all tumors were positive for CD10 and vimentin. CD29 and SMA were observed in 3 cases each (43%), and p63 and calponin in 2 cases each (29%). Other myoepithelial markers and steroid receptors were absent, except androgen receptors, which were expressed in one sarcoma. Five sarcomas showed positivity for EGFR. The distinction of specific, histogenetically defined sarcoma entities (such as leiomyosarcoma, angiosarcoma, liposarcoma) from NOS-type sarcoma with CD10 expression is usually clear-cut because the former exhibit a characteristic histomorphology and immunoprofile. Phyllodes tumors with stromal overgrowth or recurrent phyllodes tumors lacking epithelial structures as well as periductal stromal sarcomas can be ruled out by their frequent expression of CD34 and negativity for myoepithelial markers. The most important differential diagnosis is sarcomatoid metaplastic carcinoma because its treatment includes axillary lymphadenectomy. Since some NOS-type sarcomas with CD10 expression and most metaplastic carcinomas show positivity for CD29, SMA, and p63, differential diagnosis can be extremely difficult and requires extensive immunohistochemical evaluation for CKs and additional myoepithelial markers such as S-100, 14-3-3sigma, and maspin. The immunophenotype of NOS-type sarcomas with CD10 expression suggests that these neoplasms represent a mammary sarcoma variant with myoepithelial features.
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PMID:Mammary NOS-type sarcoma with CD10 expression: a rare entity with features of myoepithelial differentiation. 1662 90

Primary sarcomas of the great vessels are very rare neoplasms and only a few cases have been reported. They are divided into the two broad categories of intimal or luminal and mural sarcomas. We analysed eight advanced high-grade sarcomas originating from major vessels (seven intimal and one mural sarcoma) by means of immunohistochemistry and FISH analysis for PDGFRA, PDGFRB, EGFR and KIT receptor tyrosine kinases (RTKs), together with immunoprecipitation/western blotting, sequencing of the corresponding genes, and the search for cognate ligands. The intimal sarcomas showed a wide spectrum of morphologies and immunophenotypes, whereas the mural sarcoma had common leiomyosarcomatous features. Regardless of their category, all of the cases had a PDGFRA-deregulated cytogenetic profile mainly consisting of an amplification cluster; five were also polysomic for PDGFRB, whereas three showed disomy. Six cases had a deregulated EGFR gene, and c-Kit gene status was similar to that of PDGFRA. In one case, biochemical analysis revealed the presence of activated and highly expressed PDGFRA, PDGFRB and EGFR, whereas KIT was expressed at reference level. Sequencing of the corresponding genes revealed no activating mutations in any of the analysed receptors. The cognate ligands were detected in all cases. In predictive terms, the evidence of gene amplification/high polysomy of several RTKs, together with PDGFRA, PDGFRB and EGFR expression and phosphorylation, suggests that these tumours may be sensitive to RTK-inhibiting treatments.
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PMID:Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas. 1747 66

Overexpression of the erbB-1 (EGFR, epidermal growth factor receptor) and erbB-2 (HER2/neu) proteins contributes to the aggressive behavior of malignant tumors originating from the endometrium. We currently examined whether the trend of these proteins to overexpression is a direct effect of their gene transcriptional activities. Expression of the erbB-1/erbB-2 genes was measured applying the quantitative RT-PCR technique in 25 uterine carcinomas, 12 normal endometria, a carcinosarcoma and a case of botryoid sarcoma of the uterine cervix. We showed that erbB-1 mRNA was overexpressed in 48% (12/25) and erbB-2 mRNA was overexpressed in 8% (2/25) of the analysed tumors. The level of expression appeared to be significantly higher in the malignant tumors as compared to the benign ones for erbB-1 and for erbB-2 (p=0.0001 and p=0.008, respectively). A significant correlation between erbB-1 overexpression and tumor differentiation was found (Spearman rank correlation test, p<0.001). Concomitant erbB-1 and erbB-2 overexpression was detected only in 1 out of 25 (4%) uterine neoplasms. erbB-1 was overexpressed in a sarcoma botryoides of the uterine cervix. Our data suggest that erbB-1/erbB-2 overexpression is a direct effect of higher than normal transcriptional activity of the encoding genes in a subset of human endometrial carcinomas.
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PMID:Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium. 1754 77

Sarcomas are a heterogeneous group of malignant mesenchymal tumors of difficult classification. There is considerable variability in both histological appearance and responsiveness to therapy. Their overall poor clinical prognosis is reflected by the fact that >65% of patients suffering retroperitoneal soft tissue sarcoma die within 5 years [Heslin MJ, et al. Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management. J Clin Oncol 1997;15(8):2832-9]. A greater understanding of the biology of sarcomas is needed in order to increase the potential for identifying new therapeutic targets and strategies. Microarray analysis permits a global approach to gene expression analysis of thousands of genes at the same time and has proven to be useful for further molecular characterization of tumor tissue and cell lines. This article provides a comprehensive review of possible new biomarkers identified in gene expression studies of sarcomas. These markers give new insight into the pathogenesis of sarcomas, such as malignant fibrous histiocytoma [Lee YF, et al. Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling. Br J Cancer 2003;88(4):510-5], allow a further subclassifcation of tumors like calponin-positive and calponin-negative leiomyosarcoma, or may help to predict treatment responsiveness and prognosis in patients based on an individual gene expression pattern. In some studies candidate targets for possible new treatment strategies were identified. For instance newly identified markers such as ERBB2 [Allander SV, et al. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol 2002;161(5):1587-95] and EGFR [Nielsen TO, et al. Molecular characterization of soft tissue tumours: a gene expression study. Lancet 2002;359(9314):1301-7] might lead to the possible therapeutic use of Trastuzumab, Gefitinib or Cetuximab in synovial sarcoma, comparable to the use of tyrosine kinase inhibitor STI (Gleevec) that is the standard treatment today of CD117-positive gastrointestinal stromal tumors.
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PMID:Gene expression profiling in sarcomas. 1755 81

Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an "old-age" disease such as cancer requires an "age-old" treatment.
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PMID:Curcumin and cancer: an "old-age" disease with an "age-old" solution. 1846 66

Carcinosarcoma of the breast, often referred to as metaplastic carcinoma of the breast, is a rare malignancy with two distinct cell lines described as a breast carcinoma of ductal type with a sarcoma-like component. Clinically, carcinosarcoma of the breast is an aggressive breast cancer. The prognosis for carcinosarcoma of the breast is less favorable compared to more common types of breast cancer such as infiltrating ductal or lobular carcinoma. Currently, the evaluation of breast carcinoma includes hormone receptor analysis of the tumor tissue, with those positive for estrogen or progesterone responding better to both hormonal and chemotherapy.Trastuzumab (Herceptin(R)) is available as an adjunct treatment for tumors which over-express the HER2/neu gene. Typically, metaplastic carcinomas of the breast do not express the estrogen or progesterone receptors and do not over-express the HER2/neu oncogene. As a result of this "triple negative" phenotype, such tumors tend to be more aggressive and are unlikely to respond to targeted therapy with Herceptin. The epidermal growth factor receptor HER-1/EGFR protein is expressed in the majority of metaplastic carcinomas and thus may serve as a potential therapeutic target for EGFR inhibitors such as gefitinib and cetuximab. The two cases we describe exemplify the aggressive nature of carcinosarcoma of the breast and support the findings that this tumor type does not express the common receptors found in other breast carcinomas. These case reports also emphasize the need for investigating the role for blockade of the HER-1/EGFR receptor with targeted therapies when found to be over-expressed in the primary tumor.
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PMID:Carcinosarcoma of the breast: two case reports and review of the literature. 1912 25

Bone metastases in prostate cancer are predominantly osteoblastic. To study regulatory mechanisms underlying the establishment of prostate cancer within an osteoblastic microenvironment, human androgen-sensitive prostate carcinoma cells (LNCaP) were treated with culture medium conditioned by human osteoblast-derived sarcoma cells (OHS), and activated signalling pathways in the carcinoma cells were analyzed using microarrays with tyrosine kinase substrates. Network interaction analysis of substrates with significantly increased phosphorylation levels revealed that signalling pathways mediated by EGFR and ERBB2 were activated in LNCaP cells under OHS influence but also by androgen treatment. Activation of EGFR/ERBB2 signalling was also found in LNCaP cells in cocultures with OHS cells or osteoblastic cells that had been differentiated from human mesenchymal stem cells. Our experimental data suggests osteoblast-directed induction of signalling activity via EGFR and ERBB2 in prostate carcinoma cells and may provide a rationale for the use of EGFR or ERBB2 inhibition in systemic prevention or treatment of metastatic prostate cancer in the androgen-sensitive stage of the disease.
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PMID:Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling. 1929 21

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