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At least 19 recordsLinked to original sources
PubMed2004

Sensitivity of fresh isolates of soft tissue sarcoma, osteosarcoma and giant cell tumour cells to Apo2L/TRAIL and doxorubicin.

Chemotherapy is an established treatment modality for bone sarcomas such as osteosarcoma (OS). However, the use of chemotherapy in high-grade soft tissue sarcomas remains controversial, with the most active chemotherapeutic agent, doxorubicin (DOX), reported to have a response rate of, at best only 34% and most studies reporting lower response rates. Apo2L/TRAIL is a member of the tumour necrosis factor (TNF) family of cytokines and induces death of tumour cells, but not normal cells. Its potent apoptotic activity is mediated through cell surface death domain-containing receptors, DR4/TRAIL-R1 and DR5/TRAIL-R2. We investigated the efficacy of Apo2L/TRAIL as a single agent, and in combination with clinically relevant chemotherapeutic drugs, in fresh isolates of primary malignant cells obtained from biopsy material. The data presented here demonstrate that, in a range of primary bone related tumours, as well as soft tissue sarcomas, chemotherapeutic agents were only moderately effective, in terms of induction of cell death. Apo2L/TRAIL alone had little or no effect on any bone-related tumour or sarcoma in culture. In contrast, the combination of Apo2L/TRAIL and chemotherapeutic drugs produced a significant increase in tumour cell death, with DOX and Apo2L/TRAIL proving to be the most effective combination. These data suggest the potential for Apo2L/TRAIL to increase the effectiveness of chemotherapeutic drugs in bone and soft tissue sarcomas, while perhaps concurrently allowing a reduction in the exposure to drugs such as DOX, and a consequent reduction in toxicity. The synergistic action between these two different classes of agents has yet to be tested in vivo but may prove clinically relevant in the treatment of this refractive class of malignancies.

Adolescent↗
PubMed1998

A Southwest Oncology Group and Cancer and Leukemia Group B phase II study of doxorubicin, dacarbazine, ifosfamide, and mesna in adults with advanced osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.

BACKGROUND: Ewing's sarcomas, osteosarcomas, and rhabdomyosarcomas are significantly more responsive to chemotherapy than other sarcomas. Adjuvant chemotherapy is used routinely based on data from randomized trials. Although a percentage of children with locally advanced or metastatic tumors remain curable, few data exist regarding the tumor's natural history or response and survival in adults. METHODS: This Phase II study evaluated doxorubicin, dacarbazine, ifosfamide, and mesna (MAID) in adults with inoperable or metastatic Ewing's sarcoma, rhabdomyosarcoma, or osteosarcoma. RESULTS: Between 1987-1991, 81 patients were entered; 69 patients were eligible. One patient died of neutropenic infection. Ten patients (14%) responded completely and 34 patients (49%) had a complete or partial response. Response rates were significantly higher for patients with Ewing's sarcoma and rhabdomyosarcoma than for those with osteosarcoma (77%, 64%, and 26%, respectively; P < 0.005). Although there were no significant differences in progression free survival by histology, survival for patients with Ewing's sarcoma was significantly longer than for patients with osteosarcoma (P = 0.004.) At the time of last follow-up, 7 patients (10%) were alive without progression: 3 with Ewing's sarcoma, 1 with osteosarcoma, and 3 with rhabdomyosarcoma. CONCLUSIONS: MAID chemotherapy is an active regimen in adults with advanced or metastatic Ewing's sarcoma and rhabdomyosarcoma. Although there was no direct comparison with a doxorubicin and cisplatin-based regimen, the response rate and survival in patients with osteosarcoma suggest that doxorubicin and cisplatin-based chemotherapy would remain the accepted initial chemotherapy regimen. For patients with rhabdomyosarcoma and Ewing's sarcoma, 10-20% of patients remained disease free at 5 years.

Adolescent↗
PubMed2006

The retinoblastoma protein in osteoblast differentiation and osteosarcoma.

Osteogenic sarcoma (osteosarcoma) is the most common primary tumor of bone. It accounts for approximately 19% of all malignant tumors of the bone. Of all the molecular targets altered during the genesis of osteosarcoma, the retinoblastoma gene (RB1) shows the highest frequency of inactivation. Published data from human osteosarcoma tumors and in vivo and in vitro model systems support a role for the retinoblastoma gene family in bone development and tumorigenesis. Although a variety of bone tumors, depending on the cell of origin, including osteoclasts or osteoclast-like cells, chondroblasts, and fibroblasts, are described, for the purpose of this review we will focus primarily on the tumors arising from the osteoblast lineage.

Animals↗
PubMed2005

Case report: A rare case of Ewing's sarcoma and osteosarcoma at different sites 10 years apart.

Ewing's sarcoma of bone and osteosarcoma are rare tumors. A combination of high-grade osteosarcoma and Ewing's sarcoma of bone in anatomically unrelated sites is unique, especially in the absence of previous radiation or retinoblastoma. We present a patient with a rare case of Ewing's sarcoma of the scapula that showed no evidence of recurrence (after 10 years of continued followup) and who subsequently presented with a primary osteosarcoma of the femur.

Adult↗
PubMed1997

Li-Fraumeni syndrome in pediatric patients with soft tissue sarcoma or osteosarcoma.

Family history of cancer and features of the Li-Fraumeni syndrome (LFS) were investigated in 42 patients with soft tissue sarcoma or osteosarcoma in a pediatric hospital in Mexico City, and compared with 42 non-cancer children. Six subjects with cancer were found among 204 first-degree relatives of cancer patients while there were none among 183 first-degree relatives of non-cancer children. In three families, the proband had two affected relatives, and the type of neoplasia as well as the age of onset suggested the clinical diagnosis of LFS. Our results show that 7.1% of our pediatric patients with soft tissue sarcoma or osteosarcoma may belong to LFS families. The authors encourage pediatric and adult oncologists to pay more attention to the history of cancer in nuclear families for eventual hereditary cancer syndrome identification and cancer prevention.

Adolescent↗
PubMed1990

Magnetic resonance imaging in malignant bone tumours.

Complete removal of the tumour without leaving microscopic disease is vital in the management of bone sarcomas. Magnetic resonance imaging now seems to be the best method of depicting the changes produced by the tumour within the bone and surrounding soft tissues. In order to define its reliability, five cases of primary bone sarcomas (Ewing's sarcoma, osteosarcoma, chondrosarcoma) are described where radiographs, bone scans and magnetic resonance images are directly compared to the pathological findings after resection. We conclude that surgical margins should be redefined with respect to the extent and borders of the tumour as depicted by magnetic resonance imaging. This will allow improvement in salvage procedures, but further experience is needed so as not to jeopardize the prognosis by incomplete removal of the tumour.

Adolescent↗
PubMed2002

Measurement and analysis of the chemotherapy-induced genetic instability in pediatric cancer patients.

Bleomycin sensitivity has been proven to be a useful biomarker for environmental carcinogenesis and tumor genetic instability. We have previously reported a significant increase in the chromosomal aberrations induced by chemotherapy regimens. This study aimed to test whether there is an inherent increased genetic instability in cancer patients at diagnosis, to determine the increase and time course of the chemotherapy-induced instability and to test whether bleomycin sensitivity can be used as a predictor of tumor evolution or relapse. The analysis included 99 pediatric cancer patients with four different tumor types (Ewing's sarcoma, osteosarcoma, lymphoma and CNS tumors) and 25 controls. Blood samples (n = 171) were obtained before and at the end of treatment, during clinical remission and at relapse and bleomycin tests on lymphocyte cultures were performed. We detected a significant increase (P = 0.004) in mutagen sensitivity in patients at the end of treatment compared with untreated patients, regardless of the tumor type. In both the longitudinal and cross-sectional analyses maximal and similar values of mutagen sensitivity were found in patients during treatment (1.84 +/- 0.82) and at relapse (1.78 +/- 0.52); minimum and similar values were found in controls (0.93 +/- 0.23), untreated patients (1.15 +/- 0.65) and in those who had fulfilled the chemotherapy protocols for at least 2 years before their sample was collected (1.09 +/- 0.53). From this preliminary data we can conclude that cytostatic drugs induce a transient increase in chromosomal instability in pediatric cancer patients that can be monitored by bleomycin-induced sensitivity tests and that the genetic instability indices should be further investigated as predictors of relapse.

Adolescent↗
PubMed1996

Mediastinal mass following chemotherapy in patients with Ewing sarcoma and osteosarcoma.

Thymic hyperplasia following combination chemotherapy for malignant disease is very uncommon in adolescents and adults. Our experience includes a thymic enlargement noted on the sequential computed tomography (CT) in three patients who were disease-free after chemotherapy for Ewing sarcoma (2) and osteosarcoma (1). The development of an anterior mediastinal mass after successful chemotherapy does not always imply relapse of malignant disease. To prevent inappropriate treatment, the possibility of benign aetiology must be considered.

Adolescent↗
PubMed1990

The role of ifosfamide in the treatment of adult soft tissue sarcomas, Ewing's sarcoma, and osteosarcoma: a review.

Ifosfamide is an analogue of cyclophosphamide that has been extensively investigated in sarcomas. Like doxorubicin and dacarbazine, it belongs to the class of drugs active against advanced soft tissue sarcomas; its optimal use in combination regimens has not been identified. In the treatment of osteosarcoma and Ewing's sarcoma, ifosfamide has been identified as an effective drug. Nonetheless, in these diseases, too, its optimal place in combination therapy has not yet been determined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Biology of osteogenic sarcoma.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Despite significant clinical improvements over the past several decades through the use of combination chemotherapy and surgery, patients with metastatic or recurrent disease continue to have a very poor prognosis. Therefore, there is a continued need to study and understand the basic biology of osteosarcoma in order to devise more targeted and rational therapeutic strategies and ultimately to improve survival for these patients. This article reviews several aspects of osteosarcoma biology where data exist to suggest that specific pathways may play a role in the pathogenesis of this tumor. These areas include host genetic predispositions, tumor cytogenetics, molecular genetics (including the Rb, p53, RECQ helicase, and telomere pathways), and metastatic factors (ezrin, annexin 2, chemokine receptor 4, Fas/FasL pathways) that may contribute to both the initiation and the progression of tumor formation. Understanding the mechanisms of and interactions between the various molecular pathways that play a role in osteosarcoma pathogenesis may eventually lead to a more rational strategy for devising therapies targeted specifically toward these pathways.

Adolescent↗
PubMed2000

Bone sarcomas of the head and neck in children: the St Jude Children's Research Hospital experience.

BACKGROUND: Bone sarcomas of the head and neck are difficult to resect. The authors reviewed their institutional experience with these tumors to characterize patients' clinical findings and to assess the impact of surgical resection on outcome. METHODS: The records of the 28 patients with bone sarcomas originating in the head and neck treated at St. Jude Children's Research Hospital between March 1962 and January 1998 were reviewed. RESULTS: There were 10 males and 18 females (median age, 12.6 years) each with a single sarcoma: osteosarcoma (18), Ewing sarcoma (7), malignant fibrous histiocytoma (MFH) (2), and fibrosarcoma (1). Primary tumor sites included the maxilla (13), skull (10), mandible (2), and other sites (3). All but one patient with Ewing sarcoma had localized disease at the time of diagnosis. All patients underwent surgery: complete resection, 8; gross total resection, 4; incomplete resection, 14; and biopsy only, 2; 22 also received chemotherapy. Radiotherapy was given to all patients with Ewing sarcoma and to four patients with primary osteosarcoma. Twelve patients survived a median of 8.4 years after diagnosis, 14 died of disease, and 2 died of unrelated causes. Local disease progression was evident in 12 patients (9 with osteosarcoma, 2 with MFH, and 1 with Ewing sarcoma) who died of disease, 9 of whom had the initial treatment of biopsy alone or incomplete resection. Patients with osteosarcoma who had the initial treatment of incomplete resection or biopsy alone were more likely to experience local failure (P = 0.001) and had poorer survival (P = 0.014) than those who underwent complete or gross total resection. CONCLUSIONS: Bone sarcomas of the head and neck are rare among children and most often are localized at the time of diagnosis. Incomplete resection of osteosarcoma is associated with local failure and poor outcome. Although aggressive surgery is essential for the cure of osteosarcoma, its necessity in the treatment of Ewing sarcomas remains controversial.

Adolescent↗
PubMedDate not supplied

Intraoperative clotting factor dilution and activated hemostasis in children with Ewing's sarcoma or osteosarcoma: a prospective longitudinal study.

BACKGROUND: The study was designed to evaluate prospectively intraoperative changes in coagulation and fibrinolysis in young patients with Ewing's sarcoma (n = 12) or osteosarcoma (n = 12) who underwent major surgery, and to relate them to hematocrit (HCT) readings. MATERIALS AND METHODS: Blood samples (von Willebrand factor, fibrinogen, antithrombin III, protein C, plasminogen, t-PA ag, PAI 1 activity, F1+2, D-dimer, PAP) were obtained immediately prior to starting anesthesia, two and four hours later, immediately after surgery and on the first postoperative day. Intra- and postoperative hemostatic parameters were adjusted to preoperative HCT readings. RESULTS: Major surgery induced dilution coagulopathy due to blood product transfusion to support the patient's vascular volume. Postoperatively, VWF (0.01) and fibrinogen (0.007) were found to be significantly enhanced, whereas antithrombin III levels were significantly (0.007) decreased. D-dimer formation showed a clear, significant (0.0019) rise two hours after skin incision and remained elevated through the first postoperative day. F1+2 and PAP showed only minor deviations. T-PA (0.012) and PAI 1 (0.001) rose during the operation and normalized on the first postoperative day. Within 36 hours of the initial operation, six of the 24 patients (25%) returned to surgery to stop severe hemorrhage. CONCLUSIONS: These findings indicate that hemostatic parameters may be useful when monitoring surgery- and transfusion-induced hemostatic imbalance. Furthermore, the significant differences between the HCT-uncorrected concentration of the various plasma proteins clearly demonstrated the need to use HCT correction factors which may influence the necessity for and/or the frequency of substitution therapy with protein concentrates.

Adolescent↗