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)

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

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

Although active targeting of anticancer drugs using magnetically responsive carriers is a very attractive treatment approach for solid tumors, successful results are limited. In particular, the therapeutic utility of intravenously administered magnetically responsive carriers has to date not been clearly established. The present study investigates magnetic liposomes designed to act as anticancer drug carriers, which can be effectively delivered to solid tumors via intravenous administration. Magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) were prepared by the reverse-phase evaporation method, and an in vivo study was carried out to assess the magnetic targeting of these liposomes to hamster osteosarcoma. The average diameter of liposomes thus prepared was 146 nm. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. After the hamsters had received an intravenous administration of either magnetic ADR liposomes or ADR solution (corresponding to 5 mg ADR/kg), the ADR concentrations in plasma, tumor, liver, lung, heart, and kidney were determined at designated time intervals. Administration of magnetic ADR liposomes under magnetic force using a permanent magnet (0.4 tesla) implanted in solid tumor produced an approximately 4-fold higher maximum ADR concentration in the tumor than did administration of ADR solution. The former administration modality induced an increase in ADR concentration in the liver and lung and a decrease in the heart compared with concentrations produced by the latter. The present results indicated that intravenously administered magnetic ADR liposomes can be used to effectively deliver ADR to osteosarcoma implanted with a magnet, as well as to the lung, a common site of metastases for osteosarcoma. Our results also suggest that this new treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, can improve the clinical chemotherapy of solid tumors.
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PMID:Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters. 1089 40

To control the growth of primary tumors effectively with systemic chemotherapy, we recently developed intravenously administered small-sized magnetic liposomes as an anticancer drug carrier. We previously reported that intravenously administered magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) effectively delivered ADR to the target site where a permanent magnet was implanted. In the present study, the therapeutic efficacy of this novel treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, was further evaluated by comparing tumor growth rates among different administration modalities and by histological examination of treated tumors. Small-sized magnetic ADR liposomes with a mean diameter of 146 nm were prepared by the reverse-phase evaporation method. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. One day prior to the animal study, either a permanent magnet (with magnetic force) or non-magnetic alloy (without magnetic force) was implanted in the center of the tumors. Treatment with magnetic ADR liposomes under magnetic force showed significantly greater antitumor activity than intravenous administration of ADR solution or that of magnetic ADR liposomes without magnetic force. ADR administered as magnetic liposomes eliminated weight loss of hamsters, one of the side effects produced by ADR. Interestingly, magnetic liposomes (without incorporated ADR) given under magnetic force also suppressed the tumor growth. The selective accumulation of magnetite particles in the tumor blood vessels was observed by histological examination. These results suggest that this systemic chemotherapy can effectively control the primary tumor without significant side effects, due to the targeting of magnetic ADR liposomes.
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PMID:Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters. 1111 48

The resistance of cancer cells to chemotherapeutic agents is a major obstacle for successful chemotherapy, and the mechanism of chemoresistance remains unclear. The present study developed an adriamycin-resistant human osteosarcoma MG-63 sub-line (MG-63/ADR), and identified differentially expressed proteins that may be associated with adriamycin resistance. Two dimensional gel electrophoresis, matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis and a protein identification assay were performed. Western blot analysis was used to examine the prohibitin (PHB) levels in the MG-63/ADR cells. Quantitative polymerase chain reaction was utilized to detect adriamycin resistant-associated genes. Laser-scanning confocal microscope was employed to examine the colocalization of PHB with v-myc avian myelocytomatosis viral oncogene homolog (c-myc), FBJ murine osteosarcoma viral oncogene homolog (c-fos), tumor protein p53 and retinoblastoma 1 (Rb). In addition, the full length of the open reading frame of human PHB was subcloned into a lentiviral vector pLVX-puro. The proliferative rate of MG-63 cells was also investigated. The overall protein expression in MG-63/ADR cells was clearly suppressed. Three notable protein regions, representing high mobility group box 1, Ras homolog gene family, member A, and PHB, were identified to be significantly altered in MG-63/ADR cells when compared with its parental cells. Therefore, PHB modulated the chemoresistance of MG-63/ADR cells by interacting with multiple oncogenes or tumor suppressor genes (c-myc, c-fos, p53 and Rb). In addition, overexpression of PHB decreases the proliferative rate of MG-63 cells. In conclusion, PHB is an adriamycin resistance-associated gene, which may inhibit the proliferation of human osteosarcoma MG-63 cells by interacting with the oncogenes or tumor suppressor genes, c-myc, c-fos, p53 and Rb.
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PMID:Adriamycin resistance-associated prohibitin gene inhibits proliferation of human osteosarcoma MG63 cells by interacting with oncogenes and tumor suppressor genes. 2760 27


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