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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the growth of tumors and the expression of the protooncogene Bcl-2 could be shown in epithelial tumors. A bcl-2 expression leads to a prolonged cell survival due to an inhibition of apoptosis. The potential meaning of bcl-2 expression in mesenchymal tumors remains still unknown. The fact, that the heterogenous group of osteosarcoma is not sufficiently characterized at present, suggested to investigate the bcl-2 expression in osteosarcoma. Thus, immunohistochemistry was used to analyze 47 specimens of different osteosarcomas of 36 patients. Sixteen cases (46%) showed a strong expression of bcl-2 and 13 cases (35%) were moderately positive for bcl-2. Seven cases (19%) were negative for bcl-2. The heterogenous, negative up to strong expression of bcl-2 yield clues, that the Bcl-2 controlled regulation of programmed cell death could be an important factor of cellular kinetics. Additionally the cellular proliferation rate was determined with the monoclonal antibody MIB 1, directed against the Ki-67 epitope. The data of bcl-2 expression and cellular proliferation rate lead to a classification correlating with the histological classification. To verify the importance of apoptosis in the genesis of mesenchymal tumors and whether Bcl-2 may play an important role as a predictive factor for the prognosis of osteosarcoma, further investigations will be needed.
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PMID:[Osteosarcoma--apoptosis and proliferation. Study of bcl-2 expression]. 785 2

The expression of both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), and of their receptors (EGFR and PDGFR) was immunohistochemically examined in 37 cases of osteosarcoma. Furthermore, immunostaining for p53 protein and Ki-67 antigen by MIB-1 was carried out and compared with the above results. EGFR (81%) expressed more often than EGF (51%) and the expression of EGF and EGFR, and PDGF and PDGFR were recognized in 49% and 38%, respectively. In eleven cases (30%), the expression of both growth factors and their receptors was combined. Anaplastic osteosarcoma showed higher MIB-1 index than osteoblastic and fibroblastic subtypes (P < 0.05). High grade osteosarcomas (G3 and G4) revealed higher MIB-1 index compared with low grade tumors (G1 and G2). PDGF positive tumors (MIB-1 index: 20.0) showed significantly higher proliferation compared with PDGF negative tumors (MIB-1 index: 6.5) (P < 0.01). Five out of 37 cases (13.5%) showed positive immunoreaction for p53. There was no correlation of p53 status with MIB-1 index and the expression of growth factors or their receptors. Our results suggest that PDGF expression may be an important mediator of cell proliferation control, via an autocrine mechanism, in human osteosarcoma.
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PMID:Expression of growth factors and their receptors in human osteosarcomas. Immunohistochemical detection of epidermal growth factor, platelet-derived growth factor and their receptors: its correlation with proliferating activities and p53 expression. 854

Bone tumors represent a group of tumors of various dignity. In spite of this single tumor entities may display strong morphological resemblance to each other which can in turn result in profound difficulties in differential diagnosis. The biological behaviour of a tumor is mainly determined by its rate of proliferation. In this study the rate of proliferation of 64 bone tumors (30 high-grade central osteosarcomas, 6 low-grade osteosarcomas, 8 giant cell tumors, 8 aneurysmatic bone cysts, 5 osteoidosteomas/osteoblastomas, 7 fibrous dysplasias and 5 cases of a myositis ossificans) were analysed. Immunohistochemistry was performed on paraffin-embedded tissue sections using the MIB-1 monoclonal antibody. MIB-1 recognizes the proliferation-associated Ki-67 protein which is expressed during the active phases of the cell cycle but cannot be detected in senescent cells. Among high-grade central osteosarcomas a significantly higher rate of proliferation (average value 30%) was found in comparison with low-grade osteosarcomas and other benign intraosseous bone tumors. This approach proved to be very useful in the distinction between high-grade and low-grade osteosarcomas as well as bone-forming intraosseous tumors. However distinguishing low-grade osteosarcomas from benign bone tumors by determining only the rate of proliferation was not possible, although interestingly, the proliferative rate of myositis ossificans, a purely reactive lesion, was in the range of the values determined for high-grade osteosarcoma.
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PMID:[Cell proliferation in bone tumors. Immunohistologic study of Ki-67 protein expression]. 868 97

Ki-67 is a proliferation marker that is often used to estimate the growth fraction of tumors and other tissues. This antigen is expressed during all phases of the cell cycle but not in quiescent G0 cells. Many studies fail to indicate that the Ki-67 antigen can be expressed even when DNA synthesis is blocked. We studied the expression of the antigen Ki-67 in cycle-arrested osteosarcoma cells. We found that these cells are positive for Ki-67 even when they are arrested in G1/S or G2/M by using synchronizing inhibitors, by inducing p21(Waf1/Cip1) in a tetracycline-regulated expression system or by inducing wild type p53 and p21 after inflicting DNA damage. Our results show that not all cells containing the Ki-67 antigen are actively proliferating cells and we advise against the use of Ki-67 in studies on cells that overexpress p53 or p21.
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PMID:Positivity of the proliferation marker Ki-67 in noncycling cells. 966 19

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite sensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 (p53) and 13q14 (Rb) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss (P < 0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.
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PMID:Association of loss of heterozygosity at the p53 locus with chemoresistance in osteosarcomas. 968 58

The aim of this study was the evaluation of p53/MDM-2 protein overexpression in different subtypes of human sarcomas, and their correlation with proliferative activity and patient outcome. We selected 40 cases of human sarcomas comprising 6 malignant fibrous histiocytomas (MFH), 1 fibrosarcoma, 1 dermatofibrosarcoma protuberans, 5 liposarcomas, 9 leiomyosarcomas, 1 rhabdomyosarcoma, 3 synovial sarcomas, 2 osteosarcomas, 1 chondrosarcoma, 4 Ewing's sarcomas, 2 Kaposi's sarcomas, 1 malignant haemangiopericytoma, 1 phylloides cystosarcoma, 1 neuroblastoma, 1 chordoma and 1 unclassified sarcoma. All the immunohistochemical markers, which had been used for the characterization of these sarcomas were re-examined. Additionally, the Streptavidin-Biotin peroxidase method was performed on paraffin sections using the monoclonal antibodies: anti-p53 antibody DO7, anti-MDM-2 antibody IF2 and anti-Ki-67 antibody MIB-1. According to our results, p53 protein nuclear expression was detected in 20% (8/40) of the tumours (1 fibrosarcoma, 2 liposarcomas, 1 leiomyosarcoma, 1 rhabdomyosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). MDM-2 nuclear staining was determined in 7.5% (3/40) of the cases (1 MFH and 2 liposarcomas). A high proliferative index was demonstrated in 27.5% (11/40) of the tumours (2 MFH, 4 leiomyosarcomas, 1 rhabdomyosarcoma, 1 osteosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). p53 overexpression was associated with high tumour grade (p < 0.05) and MIB-1 expression was correlated with reduced survival (p < 0.05), but p53 overexpression was not significantly associated with either MIB-1 score or with overall survival of the patients. In conclusion, from this limited and heterogeneous sample of cases, we suggest that the p53/MDM-2 pathway is involved in the tumourigenesis of several sarcoma subtypes, but it is unclear if the overexpression of these genes may become prognostic marker for patients affected with these highly aggressive tumours.
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PMID:p53/MDM-2 immunohistochemical expression correlated with proliferative activity in different subtypes of human sarcomas: a ten-year follow-up study. 989 39

Alterations in Ki-67 activity have been associated with tumor progression and poor outcome in cancer patients. This study was undertaken to identify the potential of this proliferative marker as a predictor of pulmonary metastases (PM) and mortality in osteosarcoma patients. In 38 patients with tissue available for immunohistochemical analysis, overexpression of Ki-67 was assessed. Chi-square and log rank tests were used to determine differences between proportions of the marker with PM and mortality and survival distributions respectively. P values equal or less than .05 were considered statistically significant. The median follow up of this case series was 28 months. Eighteen (47.4%) of 38 patients developed PM, and 17 (44%) overexpressed Ki-67. We found a high frequency of PM (15 of 17) among those cases that overexpressed Ki-67. This relationship was significant (P = .000006) when compared to the rest of the group. We also found a statistically significant correlation between patients with positive and negative Ki-67 scores and higher and lower mortality (P = .000962). These findings suggest that Ki-67 overexpression could be used as a prognostic molecular marker for the development of PM in osteosarcoma patients.
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PMID:Ki-67: a proliferative marker that may predict pulmonary metastases and mortality of primary osteosarcoma. 1134 57

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling. MMPs, VEGF, Ki-67 (proliferative protein), and constituents of ECM play a critical role in angiogenesis and underlie neoplastic invasion and metastasis. This prompted us to investigate the effect of a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract (NM) on the growth of tumors induced by implanting human osteosarcoma MNNG in athymic nude mice and the expression of MMPs, VEGF, Ki-67 and fibronectin in these tumors, as well as the production of mucin (by PAS staining). We also investigated the effect of the supplemented diet on serum ascorbic acid, total protein content, alkaline phosphatase activity, and liver enzymes. Athymic male nude mice (n = 12) were inoculated with 3 x 10(6) osteosarcoma cells MNNG-HOS and randomly divided into group A (fed a regular diet) and group B (fed a regular diet supplemented with 0.5% NM). Four weeks later, the mice were sacrificed. Results showed that NM inhibited the growth and reduced the size of tumors in nude mice. Histological evaluation revealed increased mitotic index, MMP-9, and VEGF secretion in the control group tissues. Results demonstrate that the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested strongly suppressed the growth of tumors without adverse effects in nude mice, suggesting potential as an anticancer agent.
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PMID:Effect of ascorbic acid, lysine, proline, and green tea extract on human osteosarcoma cell line MNNG-HOS xenografts in nude mice: evaluation of tumor growth and immunohistochemistry. 1701 99

Low-grade central osteosarcoma is a rare type of osteosarcoma with peculiar clinical radiographic and microscopic features. The aim of this article is to report and discuss a case of low-grade central osteosarcoma in the mandible of a 42-year-old woman. The patient reported sensing mild pain and tooth mobility for a period of 4 years, despite continuous dental treatment. Radiographic evaluation showed a mixed radiopaque/radiolucenct lesion in the body, ramus, coronoid process, and condyle of the left side of the mandible. Destruction of the mandibular cortex in the area was also observed. After incisional biopsy, the patient underwent hemimandibulectomy. Microscopic findings showed a tumor exhibiting spindle cells with nuclear hyperchromasia and no mitotic activity, irregular osteoid formation, and soft tissue infiltration. The immunohistochemical analysis of the expression of Ki-67, Cyclin B1, and PCNA proteins (cellular proliferation markers) revealed a very low Ki-67+ and Cyclin B1+ cell index (mean 7% and 3%, respectively), but a moderate number of PCNA+ cells (mean 49%). The 2 years of clinical and imaging postoperative follow-up showed no evidence of recurrence. Clinicians should be aware of these lesions, because histopathologicially low-grade central osteosarcoma may be misinterpreted as fibrous dysplasia.
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PMID:Low-grade central osteosarcoma of the mandible: a case study report. 1723 43

Sex steroid receptors including estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) have been sporadically reported in human osteosarcoma or its cell lines. Therefore, sex steroids have been considered to play some roles in human osteosarcoma, but no systematic and detailed studies regarding the correlation between the status of these receptors in sarcoma cells and clinicopathological parameters have been reported. We examined the existence of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then characterized the potential influence of sex steroids on cell proliferation of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed all of these receptors. ER-beta and PR were detected in the great majority of the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not detected in all the cases, and AR was detected only in eight cases. There was a significant positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The absence of aromatase in tumors also suggests the relative importance of concentrations of circulating sex steroids. Proliferation of MG-63 cells was significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestosterone (DHT), and was significantly suppressed by the addition of fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR, respectively. Sex steroids, particularly estrogen and progesterone, are considered to play important roles in the regulation of cell proliferation in human osteosarcoma. In addition, these data suggest the potential for a novel endocrine therapy in osteosarcoma using clinically available inhibitors of progesterone and estrogen actions.
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PMID:Sex steroid receptors expression and hormone-induced cell proliferation in human osteosarcoma. 1808 79


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