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)

While structure-activity relationships for vinblastine (VLB), vincristine, deacetyl-VLB, and deacetyl-VLB amide (vindesine, VDS) in several tumor and leukemia models have been reported previously, the present study explores these relationships for a series of N-substituted vindesine analogues. These compounds were prepared from the reaction of deacetyl-VLB acid azide with the appropriate amines and were characterized by mass spectral analysis, 1H and 13C NMR spectra, electrometric titration, and infrared spectra. N-Alkylvindesines have reduced activity compared to that of VDS against the Gardner lymphosarcoma (GLS). N-beta-Hydroxyethyl-VDS surpasses vindesine in its activity against the Ridgway osteogenic sarcoma and the GLS, whereas against the B16 melanoma it is less active than VDS. N-beta-(4-Hydroxyphenethyl)-VDS, envisaged as a substrate for the enzyme tryosinase, was shown to be more active than VDS against the B16 melanoma but has only marginal activity against the GLS. In terms of collective antitumor activity against the model systems used, vindesine emerges as the congener with optimum qualities. Bis(N-ethylidenevindesine) disulfide, the first example of a bridged bisvindesine and comparable to VDS in its antitumor profile, shows evidence of activity against a P388/VCR leukemia strain known to be resistant to maytansine as well as to vincristine.
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PMID:Structure-activity relationships of dimeric Catharanthus alkaloids. 2. Experimental antitumor activities of N-substituted deacetylvinblastine amide (vindesine) sulfates. 43 Apr 77

The development and application of the VCR-MTX-CF regimens for the treatment of osteogenic sarcoma have changed the biological behavior of the tumor. Recent results strongly project major advances for the future. Although the major effect of chemotherapy resides in the eradication of micrometastases, its application for treatment of the primary tumor may also be considered. However, careful experimental design and follow-up periods for several years will be required to determine the optimum approaches. For example, it is possible that the interaction between weekly VCR-MTX-CF and radiation therapy may assume increasing importance. Thus, with the effective application of VRC-MTX-CF, the management of osteogenic sarcoma has evolved into a multidisciplinary approach and future advances will be based on the collective judgement of specialists from many fields.
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PMID:Osteogenic sarcoma: state of the art with high-dose methotrexate treatment. 108 79

The primary site of metastasis of osteosarcoma is the lung. In the past, even if the primary lesion was completely removed by radical surgery, more than 90% of patients of died pulmonary metastasis with in one to two years. Control of osteosarcoma therefore depends upon the prevention and treatment of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin and high-dose methotrexate with Leucovorin rescue, dramatically improved the prognosis of osteosarcoma. In the past where systemic chemotherapy was not available, the five-year survival rate was around 19%. The majority of patients developed bilateral pulmonary metastasis within one year after onset, and died. These patients exhibited numerous micro-metastases as well. In patients receiving surgical adjuvant chemotherapy with current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, a single metastasis appearing after the termination of treatment, or early and multiple, appearing resistant to treatment. Surgery is indicated in the former situation while some therapeutic system must be devised for the latter. Recently, preoperative chemotherapy for limb-saving is given to patients with osteosarcoma of the extremities (NSH-3, 4, 5). The adjuvant of chemotherapy proved to be of great significance for improving the survival rate of osteosarcoma and for achieving limb salvage.
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PMID:[Surgery and adjuvant chemotherapy of osteosarcoma]. 346 May 27

The primary site of the metastasis of osteosarcoma is the lung. More than 90% of patients have died of pulmonary metastasis in one to two years. Control of osteosarcoma depend upon the prevention of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin, high-dose methotrexate with Leucovorin rescue and Cisplatinum, dramatically improved the prognosis of osteosarcoma. In the past, when systemic chemotherapy was not available, the five-year survival rate was around 19%. In patients who receive chemotherapy with the current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, with a single metastasis appearing after termination of treatment (late isolated type), or early and multiple, emerging in reaction to treatment (early multiple type). It is generally accepted that post-operative chemotherapy can inhibit pulmonary micro metastasis and prove to be of great significance in improving the survival rate of patients with osteosarcoma of extremities and achieve limb salvage operation. On the other hand, effective control of the side effects of drug administration such as nausea, vomiting, alopecia, cardio (ADM) and renal (CDDP) toxicity and bone marrow suppression, is a problem that must be solved as soon as possible.
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PMID:[Significance of surgical adjuvant chemotherapy in osteosarcoma]. 349 46

A unique case of a 15-year-old boy with complete paraplegia due to the compression of osteogenic sarcoma at the fourth thoracic vertebra is presented. Because of the difficulty of surgical treatment, he was treated merely by the arterial infusion of Adriamycin (doxorubicin) and systemic chemotherapy in conformity with the cyclophosphamide, Oncovin (vincristine), methotrexate, phenylalanine mustard, Adriamycin (doxorubicin) ( COMPADRI )-III regimen. The patient regained normal function, and has been disease-free without any neurologic deficit for 6 years. There appears to be some hope for cure using chemotherapy only in otherwise unpromising patients.
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PMID:Osteogenic sarcoma of the fourth thoracic vertebra. Long-term survival by chemotherapy only. 658 74

Twenty year's (1959-1979) experience in the treatment of osteosarcoma at the Bone Tumor Center of the Istituto Ortopedico Rizzoli is presented. During this period 433 cases were recorded, but only 266 were considered. All the patients underwent surgery but after 1970 whole-lung irradiation (1971), immunotherapy (1971), and chemotherapy (1972 onward) were added as adjuvant therapies on a nonrandomized basis. In the group treated with surgery alone the prognosis was very poor: 10% survived nine years or more after the diagnosis, an average disease-free interval of 7.7 months and an average survival time of 13 months. Monolateral whole-lung irradiation had negative results and was abandoned after six cases. Adjuvant immunotherapy with irradiated autologous tumor cells gave moderately positive results in 16 patients, but only by delaying the appearance of first metastases, therefore increasing the time of survival. Adjuvant chemotherapy was performed with three different protocols: one protocol with ADM only and two protocols using VCR + MTX (at medium dose) + ADM, administered according to two different schedules. Superimposable results were obtained with these three regimens. With equal follow-up, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly higher than that of patients treated with surgery alone (P less than 0.001). The patients in the chemotherapy group who had relapses showed a prolonged time (mean = 12.3 months) to the onset of the first metastasis. Adjuvant chemotherapy caused virtually no morbidity and no deaths. Reference is made to the advantages of a large and homogeneous caseload deriving from a single institution to avoid preselection bias and evaluate the effectiveness of new therapeutic approaches when patient randomization has not been employed.
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PMID:The treatment of osteosarcoma of the extremities: twenty year's experience at the Istituto Ortopedico Rizzoli. 694 43

Recent advances in adjuvant chemotherapy for malignant bone tumor have been improving the survival rate and making limb-salvage surgery a reliable technique. Ewing's sarcoma is treated by multiple agent chemotherapy. We treat Ewing's sarcoma by Rosen's T-11 protocol (CYT.ADM.MTX.VCR.ACT-D.BLM). This protocol is very effective, but results are poorer than for osteosarcoma. Newly developed protocols such as EICESS (European Intergroup Cooperative Ewing's Sarcoma Study)-92, including new drugs, should be investigated. The results with malignant fibrous histiocytoma are comparable to those for osteosarcoma. We have performed an original chemotherapy protocol, called "K-1 protocol." Patients were treated with three courses of intraarterial infusion of cisplatin (120 mg/m2) and caffeine (1.0-1.5 mg/m2/day for three days continuously) at two-week intervals. If the effect was insufficient, ADM (30 mg/m2/day for two days continuously) is added to this protocol. We treat malignant lymphoma in collaboration with a hematologist and radiologist. The 5-year survival rate of non-Hodgkin's lymphoma in our series was 56% in clinical stage III and 34% in clinical stage IV. We are trying third-generation chemotherapy to improve the survival rate.
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PMID:[Chemotherapy for Ewing's sarcoma, malignant fibrous histiocytoma and malignant lymphoma]. 821 63

32 cases of postoperative osteogenic sarcoma treated by chemotherapy combined with Chinese medicinal herbs were compared with 26 similar cases as control group. The drugs used in chemotherapy consisted of two regimens, DDP and high-dose MTX plus VCR. The results showed that the side effects of chemotherapy in control group were consistent with literatures; while the group treated with Chinese medicinal herbs suffered less toxic effects, the difference between two groups was statistically significant. The medicinal herbs used to reduce the side effects induced by DDP was Pinellia ternata, Amomum cardamomum, Bambusa textilis, Citrus reticulata etc.; while the herbs used to alleviate the adverse effects of high-dose MTX plus VCR was Gypsum, Anemarrhena asphodeloides, Rehmannia glutinosa, Ophiopogon japonicus, Scrophularia ningpoensis, etc.
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PMID:[32 cases of postoperative osteogenic sarcoma treated by chemotherapy combined with Chinese medicinal herbs]. 833 32

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

Multidrug resistance (MDR) to chemotherapy is a major obstacle in the treatment of cancer and the resistance process is multifactorial. Studies on multidrug resistance mechanisms relied on the availability of cancer multidrug resistance cell lines that have been established. In this study we successfully established a multidrug resistance cell line MG63/VCR derived from human osteosarcoma cell line MG63 based on the induction by vincristine. MG63/VCR cells exhibited high resistance to vincristine and other anticancer drugs, accompanied by upregulated expression of MDR-associated genes MDR1, MRP1, and Bcl-2. Notably, we found that MG63/VCR cells exhibited higher migration ability compared to parental MG63 cells. Moreover, we demonstrated that LIMK1, a key regulator of actin cytoskeleton, was overexpressed at both mRNA and protein levels in MG63/VCR cells and the higher LIMK1 protein level was correlated with higher level of phosphorylated cofilin. In addition, knockdown of LIMK1 abolished the higher migration ability of MG63/ VCR cells. These results suggest that LIMK1 overexpression contributes to the invasion and metastasis of drug-resistant osteosarcoma and reveal LIMK as a novel therapeutic target for drug resistant osteosarcoma.
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PMID:Overexpression of LIMK1 promotes migration ability of multidrug-resistant osteosarcoma cells. 2271 93


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