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At least 433 records · Page 24Linked to original sources
PubMed2006

Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases.

PURPOSE: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. PATIENTS AND METHODS: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. RESULTS: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. CONCLUSION: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01).

Adolescent↗
PubMed2005

Gemcitabine inhibits viability, growth, and metastasis of osteosarcoma cell lines.

Gemcitabine (dFdCyd) is an analog of cytosine arabinoside with anti-tumor activity in several human cancers. However, the efficacy of this compound in osteosarcoma has not been fully elucidated. Here we assessed the anti-tumor activity of gemcitabine using osteosarcome cell lines. In 9 human osteosarcoma cell lines (G292, HOS, MG63, NY, SaOS, HuO, HuO-3N1, HuO9, HuO9-N2), gemcitabine at the doses of >100 nM showed significant cytotoxicity. In HOS and MG63 cell lines, gemcitabine inhibited DNA synthesis as determined by IdU labeling assay and induced apoptosis as determined by DNA fragmentation assay and May-Giemsa staining. In C3H mice inoculated s.c. with a murine osteosarcoma cell line, LM8, treatment of the mice with gemcitabine showed reduced size of the primary tumor associated with increased apoptotic cells and a virtual absence of metastatic lesions in the lung. Gemcitabine thus had anti-tumor activity on osteosarcoma cell lines both in vitro and in vivo. The result would provide a cellular basis for application of gemcitabine to patients with osteosarcoma.

Animals↗
PubMed2005

Effective osteosarcoma cytolysis using cytokine-induced killer cells pre-inoculated with tumor RNA-pulsed dendritic cells.

Osteosarcoma with distant metastases at late stage has posed a challenge for novel therapeutic modalities. The application of cytokine-induced killer (CIK) cells to osteosarcoma constitutes a promising strategy. This approach had been studied in multiple myeloma and breast cancers, where CIK cells exhibited specific cytotoxicity toward malignant cells while sparing wild-type tissues. However, the consistency of CIK cell-induced anti-tumor cytotoxicity has not been thoroughly examined. We investigated whether autologous CIK cells could effectively induce cytolysis of cultured osteosarcoma cells. In addition to the observed CIK cell-induced osteosarcoma cytolysis, the pre-incubation of CIK cells with autologous dendritic cells pulsed with tumor's total RNA further enhanced the tumor cytolysis to greater than 6-fold. The anti-tumor cytolysis was optimized in complete autologous setting, and was attenuated with allogeneic components. The advantage of the co-culture with RNA-pulsed DC was lost when high CIK cell density was employed for anti-tumor cytotoxic assay, but was maintained in purified CD3(+)CD56(+) cells isolated from the CIK cells. This finding implied that CIK cells at limited cell density could induce effective osteosarcoma cytolysis with an aid from tumor antigen presentation on dendritic cell surface.

Bone Neoplasms↗
PubMed2005

Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity.

Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion.

Bone Neoplasms↗
PubMed1983

Limb salvage procedures for children with osteosarcoma: an alternative to amputation.

Amputation remains the standard surgical management for patients with osteosarcoma. However, in carefully selected patients, eradication of the primary tumor can be achieved by En-Bloc resection of the affected bone preserving both anatomical and functional status. Our criteria for limb salvage procedures are that patients must: (1) be age 12 years or older, (2) have no angiographic or clinical evidence of neurovascular involvement, (3) have low-grade osteosarcoma and/or good response to preoperative chemotherapy, and (4) be compliant. Between November 1980 and October 1982, 32 patients with osteosarcoma of an extremity were seen. Eight patients ranging in age from 13 to 21 years underwent limb salvage procedures. Five of these had Tikhoff-Linberg procedures for upper extremity lesions, two had En-Bloc resections for distal femur lesions, and one patient had a segmental arthrodesis for a distal tibial lesion. Of these eight patients, two had low-grade parosteal osteosarcoma. Follow-up ranged from 10 to 28 months (median 16 months). The two patients with parosteal osteosarcoma received no further therapy, while the other six patients received multiple agent chemotherapy. One patient died at 18 months with bilateral pulmonary disease. None have had local recurrences. Two of the eight patients had minor skin necrosis, requiring revision subsequently. Three patients have had transient nerve palsy. All have had good functional results. With careful selection of patients by rigid criteria, limb salvage procedures can be a viable alternative to amputation.

Adolescent↗
PubMed2002

[Primary bladder osteosarcoma treated with hemicystectomy].

Primary osteosarcoma of the bladder is an extremely rare type of tumour, and less than 30 adequately documented cases have been registered. From a clinical and radiological point of view, it is impossible to distinguish from other types of bladder tumours, since despite the fact that calcification of the bladder wall is common in osteosarcoma, other bladder diseases exist which may also present calcification. Prior to primary bladder osteosarcoma diagnosis, it is vital to first rule out the existence of an skeletal origin. Differential diagnosis must be carried out essentially with other bone-forming tumours, such as carcinosarcoma and transitional cell carcinoma with bone metaplasia. Prognosis for bladder osteosarcoma is extremely pessimistic, as the majority of patients do not survive beyond 6 months, regardless of the treatment carried out. We present a case of bladder osteosarcoma treated by right hemi-cystectomy, which remains disease free after a follow-up period of one year.

Aged↗
PubMed1999

Prognostic significance of DNA ploidy pattern in osteosarcomas in association with chemotherapy.

In this study, we analysed the DNA ploidy of osteosarcomas at biopsy and attempted to clarify the relationship between DNA ploidy pattern and prognosis. Thirty patients with non-metastatic osteosarcoma of an extremity were studied. All underwent intensive chemotherapy with doxorubicin, cisplatin and methotrexate, in addition to wide tumor resection. DNA ploidy was detected by DNA cytofluorometry, using isolated and smeared cells of biopsied tumor tissue. Twelve tumors showed a diploid ploidy pattern and 18 showed a non-diploid pattern such as aneuploidy (15 tumors) and euploid-polyploidy (3 tumors). The event-free survival rate at 9 years was 63.5% in non-diploid osteosarcoma patients and 13.3% in diploid osteosarcoma patients. There was a statistically significant difference between the two groups (P = 0.0278). These results lead us to conclude that a non-diploid osteosarcoma may be more sensitive to chemotherapy than a diploid tumor.

Adolescent↗
PubMed1979

Malignant fibrous histiocytoma of bone and osteosarcoma. A comparative light and electron microscopic study.

Malignant fibrous histiocytomas are well-described tumors of the soft tissues. Recent investigations have shown that malignant histiocytoma may also occur as a primary bone tumor. However, difficulties may arise to distinguish malignant histiocytoma of bone from other malignant bone tumors, such as osteosarcoma. In the present study, the ultrastructure of five cases of malignant fibrous histiocytoma of bone is compared with that of osteosarcoma. The results show that malignant fibrous histiocytoma is composed mainly of histiocytic cells and fibroblastic cells. In addition, xanthomatous cells, undifferentiated cells, and giant cells may be observed. By contrast, the predominant cell type in osteosarcoma is the neoplastic osteoblast, characterized by abundant rough endoplasmic reticulum. Signs of matrix calcification in the intercellular matrix between the collagen fibrils are regularly observed in osteosarcoma, but not in malignant histiocytoma. From these results it is concluded that the ultrastructure of malignant fibrous histiocytoma arising in bone is morphologically identical with the soft tissue counterpart of this tumor. The components of the tumor are derived from neoplastic histiocytes. This cytogenesis differs from that of osteosarcoma, which is derived from neoplastic osteoblasts. Therefore, from the ultrastructural point of view, malignant fibrous histiocytoma of bone should be accepted as a distinct histologic entity among bone tumors.

Adolescent↗
PubMed2001

Osteosarcoma cell apoptosis induced by selenium.

An essential nutrient selenium has been reported to be a potential cancer preventive and inhibitory agent, although no exact mechanism has yet been proposed. Since little is known about the anti-proliferative effect of selenium on osteosarcoma, this issue was addressed in the present study in vitro using three osteosarcoma cell lines, and in vivo using an osteosarcoma transplantable to nude mice. Selenium inhibited the tumor growth in vitro and morphological changes indicative of apoptosis were demonstrated. Osteosarcomas in nude mice were inhibited in growth by selenium with no cytotoxic change in normal tissues. The findings suggested that selenium may offer a novel therapeutic modality for osteosarcoma.

Animals↗
PubMed2003

Telomerase, p53 and PCNA activity in osteosarcoma.

AIMS: The aim of this study was to investigate telomerase activity and to assess the correlation between telomerase activity, tumor proliferative activity and p53 overexpression in osteosarcoma tumor samples. METHODS: Using a telomerase polymerase chain reaction-enzyme-linked immunoassay based on the telomeric repeat amplification protocol method, we examined telomerase activity in 26 primary osteosarcoma specimens. P53 overexpression was identified using immunohistochemical staining, and tumor proliferative activity was assessed by immunohistochemical staining of PCNA. RESULTS: Telomerase activity was detected at a relatively low level in five of 26 osteosarcoma tissue specimens. P53 was detected in eight of 21 cases. There was no significant correlation between telomerase activity and p53 overexpression (p=0.325). There was a significant correlation between PCNA staining and telomerase activity (p=0.0075). CONCLUSION: Difference between the telomerase activity and p53 overexpression in osteosarcoma suggests that p53 and telomerase may not cooperate in tumor proliferation. Correlation of telomerase activity to PCNA expression suggests that telomerase activity may also useful for evaluate proliferative activity in osteosarcoma.

Adolescent↗
PubMed1998

Host related risk factors for canine osteosarcoma.

A case-control study using the Veterinary Medical Data Base (VMDB) was conducted to test the hypothesis that increasing height and increasing weight are important risk factors for osteosarcoma in dogs. The role of other host factors was also explored. The cases comprised 3062 purebred dogs with histologically or radiographically confirmed osteosarcoma admitted to 24 veterinary teaching hospitals in the United States and Canada between 1980 and 1994. The controls were 3959 purebred dogs with other diagnoses obtained randomly by frequency matching to cases for institution and year of diagnosis. The risk of osteosarcoma rose with increasing age, increasing body weight, increasing standard weight and increasing standard height. Compared with the German Shepherd breed, the highest risk of osteosarcomas was found for large and giant breeds, while small breeds had reduced risks. A twofold excess risk was observed among neutered dogs. Adjustment of risk estimates for standard height adjusted for standard weight, and vice versa, showed a stronger and more consistent association of osteosarcoma with increasing height than increasing weight.

Animals↗
PubMed2003

Parosteal osteosarcoma of the distal ulna. A rare tumour at a rare location: a case report.

We report a case of a histologically well differentiated, grade I, parosteal osteosarcoma of the distal ulna. The tumour's radiological and histological features are described, and the patient's course after wide en-bloc resection is detailed. Parosteal osteosarcoma is a rare low-grade malignant neoplasm. It belongs to the group of the osteosarcomas originating from the surface of the bone, representing a distinct tumour entity within this group, with defined histological and radiological features. We describe the radiological and histological characteristics of parosteal osteosarcoma and, based upon these features, present its classification. The differential diagnosis, including parosteal osteoma, myositis ossificans and osteochondroma, is also discussed. Finally, therapy and prognosis are outlined in accordance with the current literature. Wide en-bloc resection represents the mainstay of therapy offering an excellent prognosis with a 5-year survival rate of more than 90%. Incomplete resection, on the other hand, increases the risk of recurrence and dedifferentiation of the tumour. Dedifferentiation induces tumour spread and is associated with a poor prognosis equivalent to conventional osteosarcoma.

Bone Neoplasms↗
PubMed1990

Well-differentiated intra-osseous osteosarcoma in the mandible of a six-year-old child.

The case of an osteosarcoma arising in the mandible of a six-year-old child is presented. It was originally misdiagnosed as a desmoplastic fibroma, and after initial curettage continued to grow for twelve years. The differential diagnosis is presented and details of the surgical access and difficulties encountered in the surgical removal of this very large tumour are described. The relationship between pre-existing disease and osteosarcoma of the mandible is discussed, and the difficulties experienced in distinguishing between the fibro-osseous lesions and osteosarcoma of the mandible are highlighted. The case is presented as a well-differentiated, intra-osseous osteosarcoma with subsequent transformation into a high-grade, conventional osteosarcoma.

Child↗
PubMed2001

Simultaneous paired analysis of numerical chromosomal aberrations and DNA content in osteosarcoma.

Relatively little is known about the biologic relevance of numerical chromosomal changes in relation to DNA content in osteosarcoma. In this study, by using a series of human osteosarcoma cell lines, we standardized a method for the assessment, on the same nuclei specimen, of both specific chromosome copy numbers by fluorescence in situ hybridization (FISH) and the DNA content by static cytofluorometry or image cytometry. On the same cell lines, we also evaluated the DNA content by using flow cytometry and the chromosome number distribution by metaphase analysis. Comparison between these different methods showed that DNA ploidy level as determined by FISH or metaphase analysis is frequently lower than the ploidy pattern as defined by cytometric methods. By using comparative genomic hybridization, we were able to demonstrate that these discrepancies were due to the presence of several unbalanced chromosome aberrations, specifically gains and high-level amplifications, which affect the total DNA content with less effect on the total chromosome number. Thus, evaluation of DNA ploidy in osteosarcoma cells is needed for a correct interpretation of FISH or cytogenetic data concerning numerical chromosomal changes. Evaluation of tumor ploidy in a series of clinical samples demonstrated that in high-grade osteosarcoma, flow cytometry sometimes may give false results because of the presence of high proportions of contaminating, nonneoplastic cells that cannot be excluded from the flow cytometric assessment but that do not interfere with the evaluation of DNA ploidy by static cytofluorometry or image cytometry, in which only tumor cells are selected for the analysis. The possibility of using this method to evaluate, on the same nuclei sample, both specific chromosomal aberrations and DNA ploidy may allow a better determination of numerical chromosomal changes that may be relevant for the biologic behavior of osteosarcoma.

Bone Neoplasms↗
PubMed2006

Perinatal factors, growth and development, and osteosarcoma risk.

Osteosarcoma incidence patterns suggest an aetiologic role for perinatal factors, and growth and development. Osteosarcoma patients (n = 158) and controls with benign orthopaedic conditions (n = 141) under age 40 were recruited from US orthopaedic surgery departments. Exposures were ascertained by interview, birth, and growth records. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Current height and age- and sex-specific height percentiles were not associated with osteosarcoma risk. Male cases, however, appeared to have an earlier adolescent growth period, and earlier attainment of final height (OR = 7.1; 95% CI = 1.6-50 for <19 vs 19+ years), whereas earlier puberty appeared protective with ORs of 0.41 (95% CI 0.18-0.89) and 0.68 (95% CI 0.31-1.5) for developing facial and pubic hair, respectively. High birth weight was associated with an elevated osteosarcoma risk (OR = 3.9; CI = 1.7-10 for 4000 g vs 3000-3500 g), although there was no trend in risk with increasing weight. These data provide some evidence that osteosarcoma is related to size at birth and in early adolescence, while earlier puberty in male subjects may be protective.

Adolescent↗
PubMed2006

RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42/p44-MAPKs-Bcl-2 signaling independently of BMP-2 and cell differentiation.

Osteosarcoma is the most common primary bone tumour in young adults. Despite improved prognosis, resistance to chemotherapy remains responsible for failure of osteosarcoma treatment. The identification of signals that promote apoptosis may provide clues to develop new therapeutic strategies for chemoresistant osteosarcoma. Here, we show that lipophilic statins (atorvastatin, simvastatin, cerivastatin) markedly induce caspases-dependent apoptosis in various human osteosarcoma cells, independently of bone morphogenetic protein (BMP)-2 signaling and cell differentiation. Although statins increased BMP-2 expression, the proapoptotic effect of statins was not prevented by the BMP antagonist noggin, and was abolished by mevalonate and geranylgeranylpyrophosphate, suggesting the involvement of defective protein geranylgeranylation. Consistently, lipophilic statins induced membrane RhoA relocalization to the cytosol and inhibited RhoA activity, which resulted in decreased phospho-p42/p44- mitogen-activated protein kinases (MAPKs) and Bcl-2 levels. Constitutively active RhoA rescued phospho-p42/p44-MAPKs and Bcl-2 and abolished statin-induced apoptosis. Thus, lipophilic statins induce caspase-dependent osteosarcoma cell apoptosis by a RhoA-p42/p44 MAPKs-Bcl-2-mediated mechanism, independently of BMP-2 signaling and cell differentiation.

Anticholesteremic Agents↗
PubMed2000

Bystander-mediated regression of osteosarcoma via retroviral transfer of the herpes simplex virus thymidine kinase and human interleukin-2 genes.

Current treatment of osteosarcoma produces disappointing outcomes, and innovative therapies must be investigated. We have used retroviral vectors to transfer the herpes simplex virus thymidine kinase (HSVtk) and interleukin-2 genes to human osteosarcoma cells. Each gene was stably transduced and expressed; the HSVtk gene effectively conferred ganciclovir (GCV) susceptibility to transduced cells. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to GCV killing. Human osteosarcoma cells were used to develop a series of experiments in athymic nude mice to treat experimental osteosarcoma. Subcutaneously implanted mixtures of tumor cells and HSVtk vector producer cells developed into tumors that completely regressed upon administration of GCV. Subcutaneously implanted mixtures of transduced and wild-type cells showed a potent bystander effect upon administration of GCV, with complete tumor ablation when as little as 10% of the cells were HSVtk+. A significant (P < .05) antitumoral response was seen against primary tumors composed of unmodified cells when a secondary tumor of transduced cells was implanted at a distance of 1 cm, suggesting a diffusible bystander factor. The presence of interleukin-2-transduced cells improved the efficacy of treatment. A significant (P < .03) antitumoral response was seen in the treatment of established osteosarcomas by the injection of HSVtk vector producer cells.

Animals↗
PubMed2003

Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer.

To establish an effective B7-based gene therapy against osteosarcoma, we transferred B7-1/Fas chimeric gene adenovirally into poorly immunogenic osteosarcoma cells. We found that adenovirus-mediated rat B7-1/Fas gene transfer induced (i) expression of rat B7-1/Fas chimeric molecules in osteosarcoma cells, (ii) activation of murine T cells, (iii) apoptosis of murine osteosarcoma cells in the presence of anti-rat B7-1 mAb in vitro, and (iv) therapeutic effects more prominently than B7-1 gene transfer on the development of pulmonary metastasis and survival of mice. These findings collectively support the therapeutic value of adenovirus-mediated B7-1/Fas gene transfer on poorly immunogenic osteosarcoma, which is resistant to a treatment protocol using transduction of B7-1 alone.

Adenoviridae↗