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

After pulsed exposure of Dunn osteosarcoma cells (nonresistant cells) to Adriamycin (ADR) at increasing concentrations and single-cell cloning of surviving cells, ADR-resistant cells were obtained. These resistant cells expressed P-glycoprotein and had resistance more than 10 times that of their nonresistant parent cells. Compared to the nonresistant cells not exposed to pulsing electromagnetic fields (PEMF) in ADR-free medium, their growth rates at ADR concentrations of 0.01 and 0.02 micrograms/ml, which were below IC50, were 83.0% and 61.8%, respectively. On the other hand, in the nonresistant cells exposed to PEMF (repetition frequency, 10 Hz; rise time, 25 microsec, peak magnetic field intensity, 0.4-0.8 mT), the growth rate was 111.9% in ADR-free medium, 95.5% at an ADR concentration of 0.01 micrograms/ml, and 92.2% at an ADR concentration of 0.02 micrograms/ml. This promotion of growth by PEMF is considered to be a result of mobilization of cells in the non-proliferative period of the cell cycle due to exposure to PEMF. However, at ADR concentrations above the IC50, the growth rate tended to decrease in the cells not exposed to PEMF. This may be caused by an increase in cells sensitive to ADR resulting from mobilization of cells in the non-proliferative period to the cell cycle. The growth rate in the resistant cells exposed to PEMF was significantly lower than that in the non-exposed resistant cells at all ADR concentrations, including ADR-free culture (P</=0.0114). Therefore, this study suggests that PEMF promotes the growth of undifferentiated cells but progressively suppresses the growth of more differentiated cells, i.e., PEMF controls cell growth depending on the degree of cell differentiation. This study also shows the potentiality of PEMF as an adjunctive treatment method for malignant tumors.
 ...
PMID:Effects of PEMF on a murine osteosarcoma cell line: drug-resistant (P-glycoprotein-positive) and non-resistant cells. 1065 22

Morbidity resulting from the toxicity of chemotherapeutic drugs suggests that novel approaches are worthy of investigation. Development of the use of low intensity magnetic fields as an adjuvant to current treatment regimens to prevent metastatic disease may prove to be efficacious. Using a cell culture model, we have developed a magnetic field (MF) treatment that offers the possibility of lowering the therapeutic dose of these drugs and thereby reducing morbidity. Our studies have found that a low intensity (approximately 2 gauss) MF signal and a relatively low dose (0.1 microg/ml) of Adriamycin (ADR) inhibited proliferation of human osteosarcoma cells by 82%, whereas the MF and ADR acting individually caused only 19% and 44% inhibition, respectively.
 ...
PMID:Magnetic field induced inhibition of human osteosarcoma cells treated with adriamycin. 1073 5

The antiemetic efficacy of granisetron, ondansetron and tropisetron was evaluated in patients treated with cisplatin-Adriamycin (CDP/ADM) and ifosfamide (IFO) by continuous infusion (CI). In all, 90 patients with osteosarcoma were randomly assigned to receive granisetron (2 mg/m2), or ondansetron (5.3 mg/m2), or tropisetron (3.3 mg/m2) plus dexamethasone 8 mg/m2. Chemotherapy consisted of CDP (120 mg/m2, 48-h CI) followed by ADM (75 mg/m2, 24-h CI) and then, in the second cycle, delivered 3 weeks later, IFO 15 g/m2 (120-h CI). Complete protection (CP) from emesis was obtained on 59% of the 717 days of treatment, without significant differences among the three study drugs. A significantly higher rate of CP was obtained during chemotherapy with IFO than with CDP/ ADM (69% vs 44%; P<0.0001). The rate of CP declined from the first to the last day of treatment for both CDP/ADM (61% to 27%, P<0.0001) and IFO (95% to 43%) cycles (P<0.0001). When CDP/ ADM and IFO are delivered on multiple days by CI, granisetron, ondansetron and tropisetron have the same antiemetic efficacy, which declines from the first day onward through successive days.
 ...
PMID:Granisetron, tropisetron, and ondansetron in the prevention of acute emesis induced by a combination of cisplatin-Adriamycin and by high-dose ifosfamide delivered in multiple-day continuous infusions. 1073 60

Between January 1995 and December 1999, 11 patients with synchronous multifocal osteosarcoma (SMO) received neoadjuvant treatment with high-dose methotrexate, cisplatinum, Adriamycin, and ifosfamide. After primary chemotherapy in 4 patients who had only two bone localizations, it was possible to treat all tumor foci locally. The remaining patients, with more than three bones involved, were treated surgically only in 3 cases at the primary site, while secondary lesions did not receive any treatment. The final results of our study were disappointing. All patients died of the tumor 6 to 24 months after the beginning of treatment (mean 11.9 months). Nevertheless, the survival time of the 4 patients with locally treated lesions was significantly longer than the one of 7 patients in whom the secondary lesions were not locally treated (18.2 vs 9.1 months; P<0.008). It should be noted that those patients simultaneously operated on two sites, the response to chemotherapy of "primary" and "secondary" lesions was always similar. This homogeneity supports the thesis that in synchronous multifocal osteosarcoma the tumors are not multicentric in origin but represent bone-to-bone metastases from a monocentric tumor.
 ...
PMID:Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma: results in eleven cases. 1145 Aug 92

Pegylated-liposomal doxorubicin (Doxil) is a unique form of liposomal doxorubicin in which the liposomes are coated with methoxypoly (ethylene glycol), resulting in a diminished uptake by the reticuloendothelial system, leading to a longer half-life in blood and a different toxicity profile than nonpegylated liposomes. We performed a phase II study of Doxil in sarcoma. The patient population was primarily previously treated or had diagnoses considered unresponsive to chemotherapy. The initial dose per course was 55 mg/m2 every four weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Treatment was generally well tolerated. Of 214 evaluable treatment courses in 47 patients, toxicities were mild and similar to previous reports, but dose reduction was common. No definite cardiac toxicity was observed. There were: 6 osteosarcomas, 3 Ewings, 1 extraosseous osteosarcoma, 1 chondrosarcoma, 2 alveolar soft part sarcomas, 15 gastrointestinal stromal cell tumors (GIST), and 19 other soft tissue sarcomas. Three of the 47 patients received a CR or PR, although 15 of the 47 patients were felt to have derived clinical benefit from the treatment. Some responses were delayed. These data suggest that pegylated-liposomal doxorubicin has activity in this population of poor prognosis sarcoma and that this treatment is associated with modest toxicity.
 ...
PMID:Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. 1274 96

Neoadjuvant chemotherapy potentially can have an adverse effect on bone healing in distraction osteogenesis whether given before or concomitant with distraction osteogenesis. It was the purpose of the current study to determine if administration of chemotherapy before distraction adversely affects bone generation in distraction osteogenesis. Twenty-four adult dairy goats were divided randomly into two groups: a control group having distraction osteogenesis only and a chemotherapy group, receiving one course of Adriamycin before distraction osteogenesis. The animals were sacrificed at 6 weeks, 12 weeks, or 24 weeks and the lengthened tibias were evaluated by radiologic studies, biomechanical testing, and histologic analysis. All goats receiving chemotherapy showed systemic adverse effects. In a multifactorial analysis of the lengthened bones, there was no statistically significant difference between the control goats versus goats that received chemotherapy; indicating that there was no sustained inhibitory effect on bone formation by the chemotherapy. These findings suggest that a prior course of chemotherapy with Adriamycin may not be a contraindication to limb lengthening for limb salvage after resection of an osteosarcoma.
 ...
PMID:Effect of neoadjuvant chemotherapy on distraction osteogenesis in the goat model. 1518 75

The antiemetic effectiveness of 5-HT3 receptor antagonists in combination with dexamethasone in patients receiving short-term infusion chemotherapy has been well demonstrated. Less information is available about the efficacy of the same antiemetic combination in patients treated with regimens of chemotherapy in which the drugs are delivered in continuous infusion of several hours. The purpose of this study was to report the effectiveness of a double administration of antiemetic drugs in patients treated with strong emesis-inducing drugs for several days. In this study, 19 male and 13 female patients with osteosarcoma, ages 9 to 45 years, treated with chemotherapy, received intravenous tropisetron 5 mg plus dexamethasone 8 mg every 12 hours during the first two cycles of the preoperative treatment: cisplatin 120 mg/m2 over 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours and continuous infusion of ifosfamide 15 g/m2 over 120 hours. The assessment of the antiemetic efficacy was performed three times every day: from 8:00 am to 4:00 pm, from 4:00 pm to 12:00 am, and from 12:00 am to 8:00 am. The patients were followed from the beginning of the treatment until 2 hours after its end, when they were discharged from hospital. Complete protection from emesis was obtained in 80% of the 256 days of treatment: 81% during the first cycle (cisplatin 120 mg/m2 in 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours) and 79% during the second cycle (continuous infusion of ifosfamide 15 g/m2 in 120 hours). In both cycles, complete protection declined from the first to the last day of treatment (from 100% to 62% during the first cycle and from 100% to 63% during the second cycle). These results indicate that when chemotherapy is administered in a protracted infusion, higher doses of antiemetic agents are necessary to achieve acceptable antiemetic activity.
 ...
PMID:Tropisetron and dexamethasone administered twice daily for the prevention of acute emesis in patients treated with continuous infusion of Cisplatin-Doxorubicin and high-dose Ifosfamide over 48, 24, and 120 hours. 1288 24

A 16-year-old girl with a distal femur osteosarcoma became pain-free with the first treatment of methotrexate 12.5 g/m(2) and folinic acid 760 mg/m(2). She was inadvertently given 1275 mg folinic acid after the third dose. Four days later, pain and swelling recurred. Appreciating that this was "over rescue" rather than drug resistance led to the successful use of a further 8 doses of high-dose methotrexate when a suboptimal response was achieved with cisplatinum, Adriamycin, and ifosfamide. This is the first time "over rescue" has been documented in humans from high-dose folinic acid after methotrexate.
 ...
PMID:Progression of osteosarcoma after high-dose methotrexate: over-rescue by folinic acid. 1457 26

Slow-growing cell populations located within solid tumors are difficult to target selectively because most cells in normal tissues also have low replication rates. However, a distinguishing feature between slow-growing normal and tumor cells is the hypoxic microenvironment of the latter, which makes them extraordinarily dependent on anaerobic glycolysis for survival. Previously, we have shown that hypoxic tumor cells exhibit increased sensitivity to inhibitors of glycolysis in three distinct in vitro models. Based on these results, we predicted that combination therapy of a chemotherapeutic agent to target rapidly dividing cells and a glycolytic inhibitor to target slow-growing tumor cells would have better efficacy than either agent alone. Here, we test this strategy in vivo using the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) in combination with Adriamycin (ADR) or paclitaxel in nude mouse xenograft models of human osteosarcoma and non-small cell lung cancer. Nude mice implanted with osteosarcoma cells were divided into four groups as follows: (a) untreated controls; (b) mice treated with ADR alone; (c) mice treated with 2-DG alone; or (d) mice treated with a combination of ADR + 2-DG. Treatment began when tumors were either 50 or 300 mm(3) in volume. Starting with small or large tumors, the ADR + 2-DG combination treatment resulted in significantly slower tumor growth (and therefore longer survival) than the control, 2-DG, or ADR treatments (P < 0.0001). Similar beneficial effects of combination treatment were found with 2-DG and paclitaxel in the MV522 non-small cell lung cancer xenograft model. In summary, the treatment of tumors with both the glycolytic inhibitor 2-DG and ADR or paclitaxel results in a significant reduction in tumor growth compared with either agent alone. Overall, these results, combined with our in vitro data, provide a rationale for initiating clinical trials using glycolytic inhibitors in combination with chemotherapeutic agents to increase their therapeutic effectiveness.
 ...
PMID:2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo. 1472 4

Seventeen client-owned dogs diagnosed with spirocercosis-associated esophageal sarcomas were retrospectively reviewed. The most common clinical signs noticed were vomiting and/or regurgitation (94%), lethargy and depression (59%), pyrexia and anorexia (41% each). Leukocytosis (82%) and microcytic hypochromic anemia (30%) were the most common hematological abnormalities. Caudal thoracic masses were demonstrated on survey radiographs of 13/15 of the dogs and thoracic spondylitis was detected in 12/15 dogs. Spirocerca lupi eggs were detected in 2/8 patients and worms were demonstrated on 1/11 at necropsy. Ten cases underwent surgical attempt to remove the tumors. In six of them partial esophagectomy (PE) was performed and all of them survived the immediate postoperative hospitalization. Five of the cases that underwent PE also received chemotherapy after surgery (doxorubicin (Adriamycin, Upjohn)) with an average survival time of 267 days. The histopathological results of the esophageal tumors were osteosarcoma (9), fibrosarcoma (5) and undifferentiated sarcoma (1). In areas endemic to spirocercosis, regurgitation or vomiting in dogs and microcytic hypochromic anemia and neutrophilia warrant ruling out esophageal sarcomas. Proper surgical treatment could prolong the dogs' lifespan for months, and improve their quality of life.
 ...
PMID:Spirocercosis-associated esophageal sarcomas in dogs. A retrospective study of 17 cases (1997-2003). 1474 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>