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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human osteoblastic osteosarcoma was transplanted in nude mice and followed in seven serial passages. Tumor cell kinetics was analyzed by in vivo labelling with the thymidine analogue iododeoxyuridine (IdUrd). Immunohistochemistry was used to measure the IdUrd labelling index. Duration of S phase (ts) was estimated by flow cytometry. From these two parameters potential doubling time (tpot) was calculated. Cell kinetic parameters showed low variations between passages and also between xenografts in same passage. Smaller variations of ts compared to labelling index and tpot were found. tpot was generally short with an interpassageal mean of 1.3 days and CV=14.8%. All xenografts showed DNA aneuploidy (mean DNA index --1.6). Homogeneous tumor growth was indicated by low variations of volume doubling time and lag time. There was no correlation between tumor growth and cell proliferation. Histopathological characteristics of the donor patients tumor were retained during serial transplantation.
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PMID:Growth patterns and cell kinetics of human osteosarcoma xenografts in serial passages in nude mice analyzed by in vivo labelling with iododeoxyuridine. 860 61

Numerous studies have demonstrated a correlation between hyaluronan expression and the malignant properties of various kinds of cancer, and inhibition of hyaluronan production causes decreased tumor growth. Hyaluronan oligosaccharides have been shown to inhibit several tumor cell types via disruption of receptor-hyaluronan interaction. However, few studies have addressed hyaluronan with respect to osteosarcoma. In this study, we examined the effects of exogenously added hyaluronan oligosaccharides on tumorigenicity of murine osteosarcoma cells, LM-8, and human osteoblastic osteosarcoma cells, MG-63. Moreover, the critical size of oligomers needed to inhibit malignant properties was defined. Fluorescent hyaluronan oligosaccharides accumulated both on the surface of cells and in the cytoplasm, and this retention was blocked by pretreatment with an anti-CD44 monoclonal antibody. Hyaluronan octasaccharides significantly inhibited cell viability and induced apoptosis as defined by cell proliferation and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays, respectively. Octasaccharides also abrogated functional cell-associated matrices and significantly reduced the retention of endogenous hyaluronan. Further, octasaccharide treatment affected an inhibition of cell motility as well as cell invasiveness. Pretreatment of the cells with anti-CD44 antibody reduced the antitumor effect of the octasaccharides. In vivo, intratumoral injection of hyaluronan octasaccharides reduced the hyaluronan accumulation in local tumors, resulting in significant suppression of the formation of distant lung metastasis. Together these data suggest that hyaluronan oligosaccharides have potent antitumor effects functioning in part by the abrogation of hyaluronan-rich cell-associated matrices.
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PMID:Hyaluronan oligosaccharides inhibit tumorigenicity of osteosarcoma cell lines MG-63 and LM-8 in vitro and in vivo via perturbation of hyaluronan-rich pericellular matrix of the cells. 1759 72

Osteosarcoma is a rare type of cancer associated with a poor clinical outcome. Even though the pathologic characteristics of OS are well established, much remains to be understood, particularly at the molecular signaling level. The molecular mechanisms of osteosarcoma progression and metastases have not yet been fully elucidated and several evolutionary signaling pathways have been found to be linked with osteosarcoma pathogenesis, especially the hedgehog signaling (Hh) pathway. The present review will outline the importance and targeting the hedgehog signaling (Hh) pathway in osteosarcoma tumor biology. Available data also suggest that aberrant Hh signaling has pro-migratory effects and leads to the development of osteoblastic osteosarcoma. Activation of Hh signaling has been observed in osteosarcoma cell lines and also in primary human osteosarcoma specimens. Emerging data suggests that interference with Hh signal transduction by inhibitors may reduce osteosarcoma cell proliferation and tumor growth thereby preventing osteosarcomagenesis. From this perspective, we outline the current state of Hh pathway inhibitors in osteosarcoma. In summary, targeting Hh signaling by inhibitors promise to increase the efficacy of osteosarcoma treatment and improve patient outcome.
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PMID:Hedgehog signaling inhibitors as anti-cancer agents in osteosarcoma. 2598 15

Osteosarcoma, the most common malignant primary bone tumor, is currently treated with chemotherapy and surgery. The effectiveness of chemotherapy is evaluated by means of histological analysis of tumor necrosis, known as "the Huvos score". However, 25% of the patients initially considered good responders will relapse. In our practice, strong tissue heterogeneity around the residual viable cells of the osteosarcoma is observed, but this is not taken into account by the Huvos score, as it is only an average. The objective is to determine whether heterogeneity in the osteosarcoma's microenvironment can play a role in the histological response to chemotherapy. Two complementary approaches have been developed: (i) the therapeutic response to several monotherapies (ifosfamide, cisplatin, doxorubicin) has been compared to tumor growth and the necrosis levels in different preclinical syngeneic osteosarcoma models, mimicking various microenvironments by injecting the tumor cells into subcutaneous, intra-muscular paratibial, or intra-osseous sites; (ii) a retrospective analysis was performed on patients' osteoblastic osteosarcoma biopsies. Tissue localization mapping of residual live tumor cell colonies was evaluated for potential correlation with overall survival. The results of the preclinical studies showed a difference in tumor growth depending on the osteosarcoma model, with a higher rate in bone sites compared to subcutaneous tumors. For the therapeutic response, a higher response to doxorubicin was observed in the intra-osseous model compared to the intra-muscular model for tumor growth (P = 0.013) and necrosis (P = 0.007). These data strongly suggest that the microenvironment plays a role in how osteosarcoma responds to chemotherapy. The retrospective analysis showed no significant survival difference between residual cell sites, although the soft tissues may be seen as a potential negative factor.
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PMID:Bone microenvironment has an influence on the histological response of osteosarcoma to chemotherapy: retrospective analysis and preclinical modeling. 2921 54

There are three subtypes of undifferentiated human conventional osteosarcoma (HCOS): osteoblastic osteosarcoma (OOS), chondroblastic osteosarcoma (COS), and fibroblastic osteosarcoma (FOS). HCOS also exhibits heterogeneous pathological maldifferentiation in individual patients. Currently, the mechanism regulating HCOS differentiation remains unclear, and therapies are ineffective. Osteopontin (OPN) and osteocalcin (OCN) are markers of osteoblast maturation, and their expression is inhibited in HCOS. A previous study found that PLK2 inhibited TAp73 phosphorylation and consequent anti-OS function of TAp73 in OS cells with enriched TAp73. TAp73 was also reported to regulate bone cell calcification. Here, OOS was found to have higher TAp73 levels and PLK2 expression than those in COS, which is correlated with HCOS maldifferentiation according to Spearman analysis and affects patient prognosis according to Kaplan-Meier survival analysis. In the conventional OS cell-line Saos2 and in patient-derived xenograft OS (PDX-OS) cells, increased PLK2 expression owing to abundant TAp73 levels affected OPN and OCN content as measured by RT-PCR and Western blotting, and alizarin red staining showed that PLK2 affected calcium deposition in OS cells. In addition, PLK2 inhibition in PDX-OS cells prohibited clone formation, as indicated by a clonogenic assay, and sensitized OS cells to cisplatin (CDDP) (which consequently limited proliferation), as shown by the CCK-8 assay. In an established PDX animal model with abundant TAp73 levels, PLK2 inhibition or CDDP treatment prevented tumor growth and prolonged median survival. The combined therapeutic effect of PLK2 inhibition with CDDP treatment was better than that of either monotherapy. These results indicate that increased PLK2 levels due to enriched TAp73 affect osteogenic differentiation and maturation and OS prognosis. In conclusion, PLK2 is a potential target for differentiation therapy of OS with enriched TAp73.
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PMID:PLK2 modulation of enriched TAp73 affects osteogenic differentiation and prognosis in human osteosarcoma. 3234 84