Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma, the most common primary bone tumor in young adults, is characterized by local invasion and distant metastasis. But detailed mechanisms of tumorigenicity and metastasis of osteosarcoma are not well known. We report the involvement of calpains, a family of calcium-activated, cysteine proteases, in the invasive and metastatic processes of human osteosarcoma cells. By using siRNA treatment, the expression of mu- and m-calpains were downregulated in human Saos-2 osteosarcoma cells. Both the adhesive and invasive potentials were significantly attenuated in calpain siRNA-transfected human Saos-2 osteosarcoma cells. MMPs are the main factors involved in malignant tumor invasion and metastasis. siRNA of calpains also significantly inhibited the secretion of MMP-2 in Saos-2 cells. These results suggest that mu- and m-calpains are important in the invasion and metastasis of human osteosarcoma cells, and calpains might be targeted to reduce tumor progression.
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PMID:Silencing of calpain expression reduces the metastatic potential of human osteosarcoma cells. 1974 55

Soft tissue sarcomas (STS) with complex genomic profiles (50% of all STS) are predominantly composed of spindle cell/pleomorphic sarcomas, including leiomyosarcoma, myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, extraskeletal osteosarcoma, and spindle cell/pleomorphic unclassified sarcoma (previously called spindle cell/pleomorphic malignant fibrous histiocytoma). These neoplasms show, characteristically, gains and losses of numerous chromosomes or chromosome regions, as well as amplifications. Many of them share recurrent aberrations (e.g., gain of 5p13-p15) that seem to play a significant role in tumor progression and/or metastatic dissemination. In this paper, we review the cytogenetic, molecular genetic, and clinicopathologic characteristics of the most common STS displaying complex genomic profiles. Features of diagnostic or prognostic relevance will be discussed when needed.
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PMID:Soft tissue sarcomas with complex genomic profiles. 2021 54

The dysregulation of signal transducers and activators of transcription 3 (STAT3) has been reported to be associated with tumor progression, angiogenesis and metastasis. The purpose of this study was to analyze the clinical value of STAT3 expression in human osteosarcoma. First, semi-quantitative RT-PCR was performed to detect the expression of STAT3 mRNA in normal bone tissues, chondroma tissues and osteosarcoma tissues. Then, immunohistochemistry was performed to detect the expression of STAT3 protein in 76 osteosarcoma tissues and the relationship of STAT3 protein expression with clinicopathologic factors or prognosis of osteosarcoma patients. RNA interference (RNAi) technology was employed to inhibit STAT3 expression. MTT and flow cytometric assays were performed to analyze the effect of STAT3 inhibition on proliferation and apoptosis of osteosarcoma cells. Finally, the expression of STAT3-related target genes were also determined. Results showed that osteosarcoma tissues showed significantly higher expression levels of STAT3 mRNA than normal bone or chondroma tissues (P<0.05). Immunohistochemistry showed that the staining of STAT3 protein was mainly located in cytoplasm of osteosarcoma cells in osteosarcoma tissue samples. The high level of STAT3 protein was associated with poor tumor differentiation and presentation of metastasis (P=0.039 and 0.022). Moreover, the 5-year overall and relapse-free survival rates for osteosarcoma patients with high STAT3 expression were lower than those for patients with low STAT3 expression. In addition, the status of STAT3 protein expression was an independent prognostic factor for both disease-free survival (P=0.0235) and overall survival (P=0.0032). RNAi-mediated STAT3 inhibition could induce proliferation inhibition and apoptosis enhancement in osteosarcoma cells, which might be associated with inhibition of some anti-apoptosis genes. Overall, STAT3 plays crucial roles in osteosarcoma development and might become a potential molecular target for gene therapy of human osteosarcomas.
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PMID:Clinical value of signal transducers and activators of transcription 3 (STAT3) gene expression in human osteosarcoma. 2054 60

Our investigation involved 27 patients with osteosarcoma and 2--malignant fibrous histiocytoma of long tubular bones treated at the Center's Clinics (2001-2008). Two regimes were used for relapsed tumor: ifosamide up to 5-10 g/m2 (median 7.5) + carboplatin 300-750 mg/m2 (median 350) + etoposide 300-500 mg/m2 (median 450) (ICE), or doxorubicin 50-80 mg/m2 (median 60) (ICA). Surgical treatment used atypical resection of the lung or precision excision of metastasis. Median post-relapse follow-up was 18 months. When ICE was used, partial effect was reported in 3 (17.6%), stabilization--10 (58.8%), and tumor progression--4 (23.5%); ICA: partial effect--3 (25%), stabilization--6 (50%), tumor progression--3 (25%). Metastases were removed after a course of chemotherapy in 16 cases. Overall 3- and 5-year survival was 51.6 +/- 11% and 34.4 +/- 16%, respectively. Relatively more aggressive was the course of the disease in cases of early relapse (< or = 12 months), combination of local recurrence and distant metastasis and those who had not survived until a second surgical remission. Hence, timely combination therapy of relapsed high-grade osteosarcoma may secure relatively long remission in 35-40.3%.
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PMID:[Treatment of relapsed osteosarcoma. Role of chemotherapy using ifosamide and carboplatin]. 2055 2

The insulin-like growth factor-I receptor (IGF-IR) is a cell surface receptor tyrosine kinase that mediates cell survival signaling and supports tumor progression in multiple tumor types. We identified a spectrum of inhibitory IGF-IR antibodies with diverse binding epitopes and ligand-blocking properties. By binding distinct inhibitory epitopes, two of these antibodies, BIIB4 and BIIB5, block both IGF-I and IGF-II binding to IGF-IR using competitive and allosteric mechanisms, respectively. Here, we explored the inhibitory effects of combining BIIB4 and BIIB5. In biochemical assays, the combination of BIIB4 and BIIB5 improved both the potency and extent of IGF-I and IGF-II blockade compared with either antibody alone. In tumor cells, the combination of BIIB4 and BIIB5 accelerated IGF-IR downregulation and more efficiently inhibited IGF-IR activation as well as downstream signaling, particularly AKT phosphorylation. In several carcinoma cell lines, the antibody combination more effectively inhibited ligand-driven cell growth than either BIIB4 or BIIB5 alone. Notably, the enhanced tumor growth-inhibitory activity of the BIIB4 and BIIB5 combination was much more pronounced at high ligand concentrations, where the individual antibodies exhibited substantially reduced activity. Compared with single antibodies, the BIIB4 and BIIB5 combination also significantly further enhanced the antitumor activity of the epidermal growth factor receptor inhibitor erlotinib and the mTOR inhibitor rapamycin. Moreover, in osteosarcoma and hepatocellular carcinoma xenograft models, the BIIB4 and BIIB5 combination significantly reduced tumor growth to a greater degree than each single antibody. Taken together, our results suggest that targeting multiple distinct inhibitory epitopes on IGF-IR may be a more effective strategy of affecting the IGF-IR pathway in cancer.
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PMID:Combination of two insulin-like growth factor-I receptor inhibitory antibodies targeting distinct epitopes leads to an enhanced antitumor response. 2080 83

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a novel membrane-anchored matrix metalloproteinase inhibitor, have been shown to be associated with prognosis and suppress tumor progression through angiogenesis inhibition in many cancers. In this study, the expression of RECK in osteosarcoma was examined, and its clinical significance was firstly evaluated. RECK expression was immunohistochemically examined in osteosarcoma from 49 patients. By summing intensity and proportion scores, these patients were categorized as weak and strong. RECK expression in the primary tumor was strong in 27 patients (55.1%) and was weak in the rest of the patients. The 5-year survival rate of patients with RECK-strong tumor (81.5%) was significantly higher than that of patients with RECK-weak tumor (36.4%; p = 0.003). Reduced RECK expression significantly correlated with metastasis (p = 0.010) and recurrence (p = 0.004). A multivariate analysis confirmed that reduced RECK expression was an independent and significant factor to predict a poor prognosis (p = 0.017). RECK status is a useful prognostic factor in osteosarcoma, and an independent prognostic factor contributing to the determination of more adequate therapy strategies for each patient.
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PMID:Expression of matrix metalloproteinase regulator, RECK, and its clinical significance in osteosarcoma. 2097 64

Radionuclide functional imaging has become a central part of pediatric oncological practice. There have been a number of major advances in imaging technology in recent years, but multislice CT with PET is the modality generating most interest in cancer imaging. In this review, we discuss the common uses and specific issues with regard to PET-CT imaging in pediatric practice. Brain tumors form a significant percentage of pediatric oncology. Use of FDG-PET in brain tumors has helped distinguish viable, residual, or recurrent tumor from post-therapeutic changes and necrosis. High-grade tumors show high uptake of FDG at diagnosis. FDG-PET results may also not accurately correlate with tumor progression after intensive radiation therapy. FDG-PET has been applied to accurate biopsy of infiltrative tumors, tumor grading, and prognostication. Limited available data also suggest that FDG-PET findings correlate well with histopathology and clinical outcome in children. FDG uptake is generally greater in higher grade lymphomas than in lower grade lymphomas. FDG-PET reveals disease sites that are not detected by conventional staging methods, resulting in upstaging of disease with potential therapeutic review. FDG-PET is useful for assessing need for marrow biopsy, residual or recurrent soft tissue masses seen on CT after therapy. The primary role of FDG-PET in neuroblastoma is in non-MIBG concentrating tumors. [11C]-Hydroxyephedrine ([11C]-HED), an analogue of norepinephrine, and [11C]-epinephrine PET have also been used in evaluating neuroblastoma. Uptake of these tracers is demonstrated within minutes after tracer administration, an advantage over MIBG imaging. The exact roles of FDG-PET in osteosarcoma and Ewing's sarcoma are not definitive. FDG-PET may play an important role in monitoring response to therapy Another diagnostic role may be in assessing patients with suspected metastatic disease.
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PMID:PET/CT in pediatric oncology. 2113 46

Pure sarcomas of the uterine corpus are uncommon, constituting less than 3% of all malignancies at this site, and most of them are leiomyosarcomas and endometrial stromal sarcomas. Rare histotypes of homologous sarcomas and heterologous sarcomas are occasionally encountered, and the absence of significant accumulated experience with these histotypes at this location may potentially raise diagnostic and patient management difficulties. In this article, the clinicopathologic attributes of all earlier reported sarcomas of the uterine corpus other than leiomyosarcomas and endometrial stromal sarcomas are summarized. Included are embryonal rhabdomyosarcoma, pleomorphic rhabdomyosarcoma, angiosarcoma, alveolar soft part sarcoma, malignant perivascular epithelioid cell tumors (PEComas), osteosarcoma, chondrosarcoma, liposarcomatous tumors, malignant extrarenal rhabdoid tumors, Ewing sarcoma/primitive neuroectodermal tumor, and other rare histotypes. Embryonal rhabdomyosarcoma (20%), Ewing sarcoma/primitive neuroectodermal tumor (17%), angiosarcoma (14%), and pleomorphic rhabdomyosarcoma (13%) appeared to be more common than the others, although there was no single overwhelmingly prevalent histotype in the group. A subset, including embryonal rhabdomyosarcoma, alveolar soft part sarcoma, and PEComas, peak in the premenopausal years, but most of the others were observed in postmenopausal women. Favorable outcomes have been reported for the patients diagnosed with alveolar soft part sarcoma, and the prognosis for their counterparts with PEComa remains a matter of debate. Multimodal therapeutic approaches to contemporary patients with embryonal rhabdomyosarcomas have resulted in significantly improved outcomes. Unfortunately, most of the other sarcomas have been associated with rapid tumor progression and unfavorable patient outcomes. The differential diagnosis for these sarcomas is often extensive and varies by histotype, but their accurate diagnosis fundamentally requires the careful exclusion of biphasic malignancies.
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PMID:Heterologous and rare homologous sarcomas of the uterine corpus: a clinicopathologic review. 2116 39

Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. Because cancer cells utilize glucose as their primary energy substrate, the expression and regulation of glucose transporters (GLUT) may be important in tumor development and progression. GLUT expression has not been studied previously in human osteosarcoma cell lines. Furthermore, although insulin and insulin-like growth factor (IGF-I) play an important role in cell proliferation and tumor progression, the role of these hormones on GLUT expression and glucose uptake, and their possible relation to osteosarcoma, have also not been studied. We determined the effect of insulin and IGF-I on GLUT expression and glucose transport in three well-characterized human osteosarcoma cell lines (MG-63, SaOs-2, and U2-Os) using immunocytochemical, RT-PCR and functional kinetic analyses. Furthermore we also studied GLUT isoform expression in osteosarcoma primary tumors and metastases by in situ hybridization and immunohistochemical analyses. RT-PCR and immunostaining show that GLUT1 is the main isoform expressed in the cell lines and tissues studied, respectively. Immunocytochemical analysis shows that although insulin does not affect levels of GLUT1 expression it does induce a translocation of the transporter to the plasma membrane. This translocation is associated with increased transport of glucose into the cell. GLUT1 is the main glucose transporter expressed in osteosarcoma, furthermore, this transporter is regulated by insulin in human MG-63 cells. One possible mechanism through which insulin is involved in cancer progression is by increasing the amount of glucose available to the cancer cell.
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PMID:Insulin regulates GLUT1-mediated glucose transport in MG-63 human osteosarcoma cells. 2132 33

S100A4, a 10-12 kDa calcium-binding protein, plays functional roles in tumor progression and metastasis. The present study aimed to investigate the function of S100A4 in osteosarcoma (OS) metastasis, using a loss-of-function approach. Our previous expression profiling analysis revealed that S100a4 was preferentially expressed in the highly metastatic mouse OS cell line, LM8. Introducing a short hairpin ribonucleic acid (shRNA) targeting S100a4 using a newly established vector containing insulators and transposons, we established stable LM8 subclones with almost 100% silencing of endogenous S100a4 protein. These transfectants showed a significant suppression of cell migration in vitro as well as a marked reduction in their ability to colonize the lung and form pulmonary metastases in vivo following intravenous inoculation, whereas there was no significant change in cell proliferation or cell attachment to fibronectin, laminin, and type I collagen. Expression and phosphorylation of ezrin, an emerging OS metastasis-associated factor, and expression of MMPs, remained the same in S100a4-shRNA clones. In 61 human OS, immunohistochemical analysis showed that lesional cells in 85.2% samples expressed S100A4 protein, and the immunoreactivity was primarily cytoplasmic, but it also showed occasional nuclear localization. Chondroblastic and osteoblastic OS subtypes expressed more S100A4 than fibroblastic subtypes. The causative role of S100A4 in OS lung metastasis shown in the murine xenograft model, together with the high proportion of primary human OS expressing S100A4, suggest that S100A4 protein represents an important potential target for future OS therapy.
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PMID:Stable knockdown of S100A4 suppresses cell migration and metastasis of osteosarcoma. 2136 24


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