Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this experiment, the sensitivity of human osteosarcoma cells to various concentration gradients of HDMTX, VCR, CBP, MMC, VP16, PMB and their time-effect relationship were examined in vitro with MTT assay among 23 cases' fresh osteosarcoma (OS) tissues. It was found that OS was sensitive to MMC and PMB when the drug concentrations were equal to the calculated in vivo drug concentrations. When the concentrations were 5 times as high as those of the calculated in vivo concentrations, OS was sensitive to HDMTX, CBP, MMC and PMB. The positive rates of sensitivity were highest in 72 hours with an average of 55.1%.
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PMID:[Chemosensitivity test for human osteosarcoma cells]. 938 99

The anti-tumor effects of hypoosmotic solution of MTX in distilled water (DW) on Dunn osteosarcoma were evaluated in mouse air pouches. Dunn osteosarcoma cell suspension (1 x 10[5] cells in 0.1 ml of medium) was inoculated into the mouse subcutaneous air pouch that had formed 7 days after the initial injection of air. Two hours after the inoculation of tumor cells, 5 ml of various concentrations of MTX (from 0 to 1 x 10[-3] M) dissolved in DW or PBS were injected into the air pouch. Five minutes later, the entire solution in the air pouch was aspirated. The mice were sacrificed 3 weeks after the inoculation of tumor cells and the air-pouch tissue was transected in the coronal plane with the largest area of tumor mass. The sections were stained with H&E and the area was measured with the NIH Image program. The largest area of tumor mass in the air pouch treated with 1 x 10(-3) M of MTX in DW was 11.8+/-3.4 mm2 (N = 5), which was significantly (P < 0.005) smaller than that in PBS (51.7+/-8.3 mm2). These findings suggested that hypoosmotic solution in DW might augment the anti-tumor effect of MTX on sarcoma cells.
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PMID:Augmentation of anti-tumor effects of methotrexate by distilled water on Dunn osteosarcoma in mouse air pouch. 958 66

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

Methotrexate concentration was analyzed in a number of tissues of a patient of osteogenic sarcoma who had been on high-dose methotrexate therapy for nearly 6 months. Gall bladder and kidney contained the highest concentration of the drug, followed by testis, small intestine, skeletal muscle, bone marrow, lung, spleen, heart and liver. Although, compared to kidney the liver contained relatively small amount of the drug, yet nearly 1/5th of the total drug in liver was in bound form. This bound form of methotrexate is most likely associated with multiple forms of dihydrofolate reductase. The total concentration of methotrexate in kidney is 80 fold higher than the concentration of the drug in liver and 28 fold higher than the concentration in bone marrow. This suggests that in high-dose methotrexate therapy, nephrotoxicity is the more immediate threat to the patient than hepatotoxicity and bone marrow suppression.
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PMID:Accumulation of methotrexate in human tissues following high-dose methotrexate therapy. 1032 57

Ifosfamide is one of the currently available anticancer agents with a broad spectrum of clinical activity against a variety of tumors. To investigate its optimal combinations, we studied the effect of 4-hydroperoxy ifosfamide (the active form of ifosfamide) in combination with other anticancer agents against two human cancer cell lines, MG-63 (an osteosarcoma cell line) and MOLT-3 cells (a T-cell leukemia cell line). The cells were incubated for 4 days and 3 days, respectively, in the presence of 4-hydroperoxy ifosfamide and the other agent. Cell growth inhibition was determined by MTT assay. The effects of these drug combinations at the concentration producing 50% inhibition (IC50) were analyzed by the isobologram method. 4-Hydroperoxy ifosfamide showed additive effects with bleomycin, cisplatin, cytarabine, doxorubicin, etoposide, 5-fluorouracil, and mitomycin C, while it showed a protective effect with methotrexate in both cell lines. 4-Hydroperoxy ifosfamide showed an additive effect with vincristine in the MG-63 cell line, while it showed a sub-additive effect in the MOLT-3 cell line. No anticancer agents tested showed a supra-additive effect with 4-hydroperoxy ifosfamide. These data suggest that ifosfamide is advantageous for simultaneous administration with a majority of the anticancer agents we studied. Methotrexate is an inappropriate drug for simultaneous administration with ifosfamide.
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PMID:Effects of 4-hydroperoxy ifosfamide in combination with other anticancer agents on human cancer cell lines. 1037 Jan 65

Until the 1970s, the survival rate of osteosarcoma patients was less than 20%. By the 1990s, this had improved to 60% to 70%, and limb-sparing procedures have replaced amputation in many patients thanks to effective combination therapy. Neoadjuvant chemotherapy has become an accepted practice in the majority of institutions using protocols which include MTX, ADR, BCD and CDDP as the most active agents against this disease. Newer agents, particularly IFM and ETP, are increasingly incorporated into complex regimens. While several studies have reported multivariate analyses to identify prognostic factors, the histologic response to preoperative chemotherapy remains the most important prognostic factor. Pulmonary metastases are the primary cause of death in patients with osteosarcoma. Although current treatment regimens allow effective salvage therapy for the patients with pulmonary metastases, the actuarial survival rate is 30%. A more effective systemic treatment for those patients is needed. The current management of osteosarcoma is critically reviewed and a treatment strategy is proposed for discussion.
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PMID:[Combined multimodal therapy for osteosarcoma--neoadjuvant chemotherapy]. 1043 78

A 17-year-old boy suffered from osteosarcoma in his left distal femur. He was treated with 4 courses of HD-MTX preoperatively, then a wide resection and replacement with endprosthesis was performed. After surgery, 4 more courses of HD-MTX were administered. In the last course of HD-MTX, the serum level of MTX had not decreased to a safe level after 48 hours following MTX administration. Liver and renal dysfunction then occurred, so massive leucovorin rescue and hemoperfusion were done. Fortunately, all complications disappeared. The patient is alive and well, and has been disease free for six years since surgery.
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PMID:[Toxicosis of high-dose methotrexate (HD-MTX) for osteosarcoma, cured with treatment by leucovorin (LV) rescue and hemoperfusion--a case report]. 1074 Jun 44

The results of the Rizzoli IOR/OS-3b neoadjuvant protocol for the treatment of osteosarcoma of the extremity are reported. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate (HDMTX i.v.), followed by a combination of cisplatin (CDP i.a.)/ doxorubicin (ADM i.v.). Postoperatively all patients, regardless of the histologic response, received 3 more cycles of MTX, CDP/ADM alternated with 3 cycles of ifosfamide. In the study performed between January and December 1992 43 patients were enrolled and limb salvage was performed in 39 of them (91%). The histologic response to chemotherapy was good (90% or more tumor necrosis) in 24 patients (56%) and poor (less than 90% tumor necrosis) in 19 (44%). With a minimum follow-up of 7 years, 23 pts (53%) remained continuously free of disease, 19 relapsed and one died due to unrelated cause. In spite of the high number of limb salvages performed, only 2 local recurrences were registered. The 7-year event-free survival and overall survival were, respectively, 53% and 68%. The hematopoietic and extrahematopoietic toxicity experienced by the patients during the entire treatment was relatively mild. These long-term results confirm that, with neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with osteosarcoma of the extremities, avoiding amputation in most of them. These results, however, are no better than those achieved in our previous study IOR/OS-3a, in which only poor responder patients received ifosfamide during the postoperative treatment.
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PMID:Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol. 1123 8

Methotrexate covalently bound to human serum albumin in a 1:1 molar ratio (MTX-HSA) is a new macromolecular drug which is currently being studied in phase I clinical trials by the German Association for Medical Oncology (AIO) Phase I/II study group. Previous studies have shown that MTX-HSA differs favorably from unbound MTX in terms of plasma half-life time, tumor accumulation of albumin and uptake mechanisms into cancer cells. To achieve optimal drug efficacy, repeated treatment cycles were necessary. To evaluate the anti-tumor activity of MTX-HSA and MTX in pre-clinical in vivo models, we selected 7 solid human tumor xenografts growing s.c. in nude mice and administered drug either i.p. or i.v. weekly for 3 weeks. The maximal tolerated dose (MTD) of MTX-HSA in nude mice was 12.5 mg/kg given i.p. on days 1, 8 and 15, whereas the MTD for free MTX was 100 mg/kg given i.v. MTX-HSA was significantly more active (p > 0.01) than MTX in 3 models. In the soft tissue sarcoma SXF 1301, MTX-HSA effected complete remission/cure after a single injection, whereas free MTX resulted in short-lasting, partial tumor regression. In the prostate-cancer model PRXF PC3M, MTX-HSA produced growth inhibition of 92.8% of control or an optimal test/control (T/C) of 7.2% compared to a T/C of 20.8% for MTX (p = 0.05). In the osteosarcoma model SXF 1410, optimal T/C values were 10.2% and 14.5%, respectively (p = 0.025). In lung cancers LXFE 409 and LXFL 529, bladder cancer BXF 1258 and breast cancer MAXF 449, both compounds were inactive. The improved therapeutic effects seen in 3 xenograft models under MTX-HSA treatment are promising and might be due to specific accumulation of the compound in solid tumors owing to their enhanced permeability and retention effect. Thus, clinical development of MTX-HSA will continue and sarcomas as well as prostate cancers will be included as potential target tumors for upcoming clinical phase II trials.
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PMID:Pre-clinical evaluation of a methotrexate-albumin conjugate (MTX-HSA) in human tumor xenografts in vivo. 1134 May 78

Subacute transient cerebral dysfunction following high-dose methotrexate occurred during neo-adjuvant chemotherapy for an eighteen-year-old male with osteosarcoma in his right femur. The variety of symptoms including hemiparesis and hesitancy of speech occurred 8 days after an administration of high-dose methotrexate (10 g/m2). Evaluations including CT scan of the brain, hemogram and blood chemistry revealed no abnormal findings. The patient found it difficult to sit, speak and eat, but was not confused. He improved in a few days without any specific treatment or residual sequelae. This syndrome was transient and did not recur when he had two additional HD-MTX treatments. The cause of this syndrome remains unknown and does not seem to be predictable. It is, thus, necessary for oncologists to take due care with regard to this syndrome in HD-MTX chemotherapy.
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PMID:[A case of subacute transient cerebral dysfunction in a osteosarcoma patient following high-dose methotrexate]. 1191 42


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