Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chondrosarcoma is a primary bone tumor that has several different grades and variants. We evaluated 48 chondrosarcomas for p53 overexpression and p53 mutations. p53 expression was evaluated with immunohistochemistry using monoclonal antibodies PAb421, PAb1801, and PAb240. p53 mutations were identified with single-strand conformational polymorphism (SSCP) and DNA sequencing in selected cases. Immunohistochemistry revealed nuclear staining with PAb421 and PAb1801 in the spindle cell portion of one dedifferentiated chondrosarcoma. SSCP analysis was abnormal only in the case with positive immunostaining and localized the mutation to exons 7 and 8. DNA sequence analysis identified a point mutation of G to C in codon 276, resulting in an amino acid substitution of proline for alanine. This point mutation has been reported previously in other tumors but not in chondrosarcoma. Assimilation of our results with previous studies suggests that p53 mutations are present in a minority of chondrosarcomas but when present, are in higher grade chondrosarcomas and their variants.
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PMID:p53 mutations in chondrosarcoma. 964 35

Chondrosarcoma is the third most common primary malignancy of bone, affecting primarily the pelvic and shoulder girdles and being extremely rare in the spine. Herein, we present a case of a 65-year-old woman with a rare chondrosarcoma of the spine, who presented with clinical symptoms from the lung metastasis. The neoplasm was grade II and exhibited overexpression of the p53 tumor suppressor protein. The latter has been associated with a high propensity for distant metastases.
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PMID:Chondrosarcoma of the spine: a rare case with unusual presentation. 1707 93

Chondrosarcoma is a rare flat bone neoplasm. Herein, we present the clinicopathological and immunohistochemical findings of a case affecting the periodontum. A 16-year-old girl presented a painless reddish mass in the lower anterior gingiva. Radiographs showed bone affected by vertical and horizontal loss and enlargement of periodontal space. The histopathological features showed atypical cartilage arranged in lobules compatible with chondrosarcoma. Immunohistochemistry showed that tumor cells were immunoreactive for the anti-vimentin and S-100 antibodies. Moreover, no tumor cells had been immunostained by anti-p53. Treatment consisted of chemotherapy, followed by radical surgery and postsurgery treatment with an association of radio and chemotherapy. After one year, no signs of recurrence have been observed.
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PMID:Chondrosarcoma involving the periodontum: clinicopathological and immunohistochemical features of a case study. 1726 93

Chondrosarcoma is the second most common primary bone tumor and it responds poorly to both chemotherapy and radiation treatment. In this study, we investigated the anticancer effects of a new benzimidazole derivative, 2-(furanyl)-5-(piperidinyl)- (3,4,5-trimethoxybenzyl) benzimidazole (FPipTB) in human chondrosarcoma cells. FPipTB-induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353) but not in primary chondrocytes. Furthermore, it triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels. Treatment of chondrosarcoma cells with FPipTB was associated with increased intracellular levels of ASK1, p38, p53, and Bax, followed by release of cytochrome c from mitochondria and activation of caspases. It is also known that ER stress activates apoptosis signal-regulating kinase 1 (ASK1), which mediates activation of JNK and p38 pathways. We also found that FPipTB-induced p38 and p53 phosphorylation and upregulated Bax expression. To study the mechanism of Bax upregulation, we determined that Bax promoter activity was increased in FPipTB-treated cells, leading to an increase in intracellular levels of Bax. In addition, cell treated with Ca(2+) chelator or p38 inhibitor showed reduced transcriptional activity. The results further suggest that FPipTB triggered ER stress, as indicated by changes in cytosolic calcium levels and activated the ASK1-MKK3/6-p38-p53-Bax pathway, causing chondrosarcoma cell death. Importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 d of treatment. Thus, FPipTB may be a novel anticancer agent for the treatment of chondrosarcoma.
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PMID:FPipTB, a benzimidazole derivative, induces chondrosarcoma cell apoptosis via endoplasmic reticulum stress and apoptosis signal-regulating kinase 1. 2159 2

Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. Surgical treatment leads to severe disability with high rates of local recurrence and life threat. Curcumin, an active compound in turmeric and curry, has been proven to induce tumor apoptosis and inhibit tumor proliferation, invasion, angiogenesis, and metastasis of cancer cells. In this study, we investigated the anticancer effects of curcumin in human chondrosarcoma cells. Curcumin induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353) but not in primary chondrocytes. Curcumin induced upregulation of Fas, FasL, and DR5 expression in chondrosarcoma cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced curcumin-induced cell death. In addition, p53 involved in curcumin-mediated Fas, FasL, and DR5 expression and cell apoptosis in chondrosarcoma cells. Most importantly, animal studies revealed a dramatic 60% reduction in tumor volume after 21 days of treatment. Thus, curcumin may be a novel anticancer agent for the treatment of chondrosarcoma.
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PMID:Curcumin induces cell apoptosis in human chondrosarcoma through extrinsic death receptor pathway. 2252 53

Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagnostic marker, it is often difficult to distinguish benign tumors from low-grade chondrosarcoma. Therefore, it is necessary to search for a potential marker that has diagnostic and prognostic values in chondrosarcoma. In this study, we demonstrated by immunohistochemistry that elevated leukemia/lymphoma-related factor (LRF) expression was associated with increased malignancy in human chondrosarcoma tissue microarrays. Moreover, siRNA depletion of LRF drastically reduced proliferation of chondrosarcoma cell lines and effectively induced senescence in these cells. This could be attributed to the observation that LRF-depleted cells were arrested at the G(1) phase, and had increased p53 and p21 expression. Moreover, LRF depletion not only drastically reduces the cellular migration and invasion potentials of chondrosarcoma cells but also sensitized these cells to the apoptosis-inducing chemotherapeutic agent doxorubicin. We conclude that LRF is a survival factor in chondrosarcomas and its expression correlates with tumor malignancy and chemoresistance. Our data implicate the potential role of LRF as both a diagnostic marker and therapeutic target for chondrosarcomas.
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PMID:The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance. 2284 80

Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central chondrosarcomas. However, there has been little systematic genomic analysis of this tumor type, and, thus, the contribution of other genes is unclear. Here we report comprehensive genomic analyses of 49 individuals with chondrosarcoma (cases). We identified hypermutability of the major cartilage collagen gene COL2A1, with insertions, deletions and rearrangements identified in 37% of cases. The patterns of mutation were consistent with selection for variants likely to impair normal collagen biosynthesis. In addition, we identified mutations in IDH1 or IDH2 (59%), TP53 (20%), the RB1 pathway (33%) and Hedgehog signaling (18%).
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PMID:Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma. 2377 Jun 6

Chondrosarcomas are cartilage-forming, poorly vascularized tumors. They represent the second malignant primary bone tumor of adults after osteosarcoma, but in contrast to osteosarcoma they are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. Few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish new cell lines and animal cancer models from human chondrosarcoma biopsies to study their chemoresistance. Between 2007 and 2012, 10 chondrosarcoma biopsies were collected and used for cell culture and transplantation into nude mice. Only one transplanted biopsy and one injected cell line has engrafted successfully leading to conventional central high-grade chondrosarcoma similar to the original biopsies. In culture, two new stable cell lines were obtained, one from a dedifferentiated and one from a grade III conventional central chondrosarcoma biopsy. Their genetic characterization revealed triploid karyotypes, mutations in IDH1, IDH2, and TP53, deletion in CDKN2A and/or MDM2 amplification. These cell lines expressed mesenchymal membrane markers (CD44, 73, 90, 105) and were able to produce a hyaline cartilaginous matrix when cultured in chondrogenic three-dimensional (3D) pellets. Using a high-throughput quantitative RT-PCR approach, we observed that cell lines cultured in monolayer had lost expression of several genes implicated in cartilage development (COL2A1, COMP, ACAN) but restored their expression in 3D cultures. Chondrosarcoma cells in monolayer were sensitive to several conventional chemotherapeutic agents but became resistant to low doses of mafosfamide or doxorubicin when cultured in 3D pellets, in parallel with an altered nucleic accumulation of the drug. Our results indicate that the cartilaginous matrix produced by chondrosarcoma cells may impair diffusion of several drugs and thus contribute to chemoresistance. Therefore, 3D chondrogenic cell pellets constitute a more relevant model to study chondrosarcoma chemoresistance and may be a valuable alternative to animal experimentations.
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PMID:New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance. 2395 80

Chondrosarcoma is a malignancy of the mesenchymal tissue derived from transformed cells that produce the cartilage matrix. In the neck area, it represents less than 0.5% of malignant tumor pathology. Chondrosarcoma of the hyoid bone is extremely rare, only 20 cases having been published so far (PubMed 2014). We present the case of a 30-year-old patient from the urban area, admitted in the ENT (Ear, Nose & Throat) Emergency Service with inspiratory dyspnea, dysphagia, stomatolalia, with evolutive and progressive clinical history of 2-3 months. Endoscopic examination revealed a pharyngolaryngeal tumor process located in the right vallecula, who by mass effect displaces the above-hyoid epiglottis. CT (computerized tomography) scan described a cervical polycystic tumor aspect, with multiple septae and inside calcifications with a diameter of 3-4 mm. Surgery consisted in removal of the tumor process together with the hyoid bone. Histopathological and especially immunohistochemical examination established the diagnosis of low-grade chondrosarcoma of the hyoid bone. For assessment of the phenotype of the tumor cells, the following immunohistochemical markers were used: p53, Ki67. The patient followed radiochemotherapic oncological treatment and returned for regular follow-ups. There was a positive development with no signs of regional or remote relapse or metastasis for 24 months after surgical treatment. Surgery is the treatment of choice, with complete removal of the tumor, with chemoradiation playing an adjuvant role. Regular tracking of the patient is mandatory.
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PMID:Chondrosarcoma of the hyoid bone: a case report. 2642 77

Chondrosarcoma (CHS) is the second most common malignant bone sarcoma with increased risk of invasion and metastasis. However, the regulatory mechanisms of CHS tumorigenesis remain unknown. Here we investigated the novel role of miR-497 in regulating chondrosarcoma cell growth and cell cycle arrest. RT-PCR analysis showed that the expression of miR-497 is aberrantly downregulated in human chondrosarcoma samples and cells. After transfection with miR-497 mimic or antagomir, the proliferation and apoptosis of JJ012 and OUMS-27 chondrosarcoma cells were determined by CCK-8 assay and flow cytometric analysis, respectively. Results showed that the proliferation capacity of JJ012 and OUMS-27 cells was significantly decreased by miR-497 overexpression but increased by miR-497 repression. Apoptosis in both cell types was remarkably enhanced by miR-497 mimic but inhibited by miR-497 antagomir. By bioinformatics and luciferase reporter analysis, Cdc25A was proven to be a direct target of miR-497 in chondrosarcoma cells. Further studies indicated that miR-497 modulates the growth of chondrosarcoma cells by targeting Cdc25A, in which the cell cycle inhibitor p21 is involved through a p53-independent pathway. In conclusion, we demonstrated that miR-497 represents a potential tumor suppressor in human chondrosarcoma that regulates the growth of chondrosarcoma cells by targeting Cdc25A. This may provide a novel therapeutic target for chondrosarcoma.
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PMID:miRNA-497 Negatively Regulates the Growth and Motility of Chondrosarcoma Cells by Targeting Cdc25A. 2705 44


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