Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1522083 (Osteosarcoma)
 2,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma includes several distinct varieties. It is therefore essential to rely upon a very specialized pathologist. It is necessary to stage the tumor and to histologically define the oncologic quality of the surgical removal (surgical margins). The limb salvage surgery in osteosarcoma involves several areas of risk: the biopsy, the extension of the tumor in the marrow spaces and canal, the impingement or plugging of the vessels by the tumor, the invasion of the joint tissues, the contamination of the joint space and/or soft tissue compartments. The reconstruction after bone segmental resection involves many problems, including long-lasting prostheses, bone bank, microsurgical techniques--the preoperative chemotherapy dramatically reduced the need for amputation, in favour of conservative surgery. A good response to chemotherapy (almost total necrosis of the tumor), is the most important factor correlated with a favorable prognosis. The more recent protocols aim to increase the tumor response and the survival rate through a very intense primary chemotherapy, using Adriamycin, high-dose Methotrexate, Cisplatin and Ifosfamide.
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PMID:[Osteosarcoma]. 141 68

The successful treatment of metastases will have to include modalities that can overcome the obstacles presented by the heterogeneous nature of malignant neoplasms and the continuous evolution of variant cells. Macrophages activated to become tumoricidal by interaction with L-MTP-PE may be able to accomplish this. Osteosarcoma appears to be an ideal disease in which to employ L-MTP-PE as an additional adjuvant to present chemotherapy regimens. The lung is the most frequent site of metastases, and pulmonary micrometastases are considered to be present in the majority of patients at diagnosis. Approximately 40% of patients with osteosarcoma develop pulmonary metastases despite the administration of adjuvant chemotherapy. The 2-year disease-free interval has not improved over the past 10 years, despite multiple changes in adjuvant regimens. These data argue that there is a subpopulation of patients who harbor tumor cells that are relatively resistant to all chemotherapy. Unfortunately, this group of patients cannot be identified at the time of initial diagnosis. This necessitates the incorporation of new forms of therapy into the adjuvant chemotherapy protocols for all patients in the hope of eradicating the resistant cells harbored in the 40%. Based on the data summarized previously, L-MTP-PE may improve the clinical outcome of patients with osteosarcoma by activating pulmonary macrophages to destroy residual tumor cells that are not eliminated by chemotherapy. Monocytes from osteosarcoma patients can be rendered cytotoxic to tumor cells by in-vitro incubation with L-MTP-PE and following the intravenous administration of this agent. L-MTP-PE can be given safely to both adults and children with minimal side effects. The whole-body distribution of 99mTc-labeled liposomes containing MTP-PE confirms that the agent is taken up by the lungs. Biologic activity in osteosarcoma patients is revealed by the elevations in plasma levels of several cytokines plus stimulation of monocyte-mediated cytotoxicity following L-MTP-PE infusion and by histologic changes in the pulmonary lesions. Ifosfamide therapy given in combination with L-MTP-PE does not suppress this immune response, as judged by both plasma cytokine levels and tumor histology. Finally, L-MTP-PE has been shown to be effective as a single agent against relapsed osteosarcoma. It is unlikely that the addition of other chemotherapeutic agents to the adjuvant chemotherapy protocols will alter the 65% to 70% 2-year disease-free survival rate associated with osteosarcoma. The preceding data indicate that L-MTP-PE is an active agent against this disease and deserves further investigation. Therefore, the inclusion of L-MTP-PE with chemotherapy is a reasonable alternative to consider to improve the response rate of this disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide. 749 Feb 49

Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage surgery + adjuvant therapy) improved the patients' overall survival and quality of life. We evaluated the efficacy and feasibility of pre-operative chemotherapy with intra-arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence pattern and the survival impact based on the histologic response of pre-operative chemotherapy. Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histologic tumor response, if the tumor necrosis was >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16 360 mg/m2/3 d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. Of 41 patients, 37 patients were evaluable for efficacy and toxicities, because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 were female with median age of 16 years (range 8-41). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27.8%, grade IV 17; 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lung. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To improve the survival rate, the possible role of good salvage chemotherapy with a non-cross resistance regimen in poor responders should be evaluated.
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PMID:Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma. 1020 5

Osteosarcoma is a rare primary bone tumor, which mainly affects children and adolescents and has a poor prognosis, especially for patients with metastatic disease. A poor therapeutic response to the conventional chemotherapy is observed with the development of lung metastases, highlighting the need for improving the current regimens and the identification of early markers of the recurrent and metastatic disease. Circulating Tumour Cells (CTCs) play a key role in the metastatic process and could be powerful biomarkers of the progressive disease. The present study aimed to isolate CTCs by using a pre-clinical model of human osteosarcoma and to monitor their kinetic of release and their modulation by ifosfamide. CTCs were detectable into the bloodstream before any palpable primary tumors. Ifosfamide increased CTCs count and in contrast decreased the number of lung tumor nodules. On established tumors, ifosfamide slowed down the tumour growth and did not modulate CTC count that could be explained by a release of cancer cells from the primary tumour with reduced properties for inducing lung metastases. This report highlights the biological interest of CTCs in osteosarcoma.
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PMID:Isolation of circulating tumor cells in a preclinical model of osteosarcoma: Effect of chemotherapy. 3012 35