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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine patients with osteosarcoma were treated by chemotherapy combined with caffeine and surgery. All primary tumors showed complete histological response to preoperative chemotherapy consisting of three intraarterial infusions of cisplatin and caffeine without/with doxorubicin and two systemic high-dose methotrexate combined with vincristine. Limb-salvage surgery was performed in eight patients with marginal procedure, which led to the preservation of good limb function. Below-knee amputation was done in one patient with calcaneal osteosarcoma. There has been neither local recurrence nor lung metastasis in seven patients with conventional osteosarcoma during a median follow-up period of 28 months. Lung metastases leading to death were observed in one patient with small-cell osteosarcoma despite complete destruction of the primary tumor by preoperative chemotherapy. Chemotherapy combined with caffeine administration deserves further extensive and large-scale study in osteosarcoma.
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PMID:Effect of chemotherapy combined with caffeine for osteosarcoma. 151 77

Recently, it has been revealed that anticancer effects are increased by the inhibition of DNA repair of cancer cells. Methylxanthine is the drug which block DNA repair. In this study we discussed the combined effects of CDDP and caffeine or pentoxifylline using human osteosarcoma cells (OST strain). When 2 mM caffeine was added before 1 hr exposure of CDDP or caffeine and CDDP was added simultaneously for 1 hr, no synergistic effect was shown. On the other hand, marked synergistic growth inhibition was observed when caffeine or pentoxifylline was added continuously after 1 hr exposure of CDDP. The addition of caffeine from 24 hr to 48 hr after 1 hr exposure of CDDP also showed synergistic effects as the doubling time of OST cells was about 30 hrs. Further more we treated three patients with advanced osteosarcomas by the combination of CDDP, ADM, and caffeine (p.o.) or that of CDDP and caffeine. A nine-year-old boy with multicentric osteosarcoma treated by the combination of CDDP, ADM, and caffeine showed partial response, and caffeine did not increase the side effects of anticancer agents. Hence the study on overcoming drug resistance by the inhibition of DNA repair will be promising.
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PMID:[DNA repair and drug resistance: enhancement of the effects of anticancer agents by DNA repair inhibitors]. 270 88

A nontoxic dose of caffeine enhanced the cytotoxicity of cisplatin in human osteosarcoma cells (OST strain). Synergistic cytotoxicity was seen in vitro in OST cells when 2 mmol caffeine was added to a nontoxic dose of cisplatin (2 micrograms/ml). Caffeine reduced S-phase, G2/M-phase, and S-and-G2/M-phase accumulation by cisplatin on the DNA histogram, and nuclear fragmentation of tumor cells was frequently observed. Flow cytometric analysis appeared to be useful in assessing the efficacy of the combination of cisplatin and caffeine. The antitumor effect of the combination of cisplatin and caffeine was examined in OST transplanted to BALB/C athymic mice. Regression of the tumor was observed when cisplatin was given at a dose of 10 mg/kg. When 4 mg of caffeine was given once a day for three days after the administration of cisplatin, marked regression of the tumor was observed in groups treated with 5 or 10 mg/kg of cisplatin, without significant weight loss. These results indicate that caffeine enhances the antitumor effect of cisplatin on transplanted osteosarcoma in BALB/C athymic mice.
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PMID:Enhancement of cytocidal and antitumor effect of cisplatin by caffeine in human osteosarcoma. 272 Jul 27

A study on the effect of anti-tumor agents combined with caffeine on sarcoma cells was carried out by clonogenic assay. The materials used were an established line of human osteosarcoma cells (OST strain) and twelve surgically resected or biopsied specimens. Caffeine showed a marked synergistic effect on sarcoma cells with the DNA-damaging agents, ADR, CDDP, CPM and MMC in terms of colony inhibition. In particular, 0.2 micrograms/ml CDDP with 2 mM caffeine showed a considerable synergistic effect on human sarcoma cells. Among the 12 cases, more than 50% colony inhibition was observed in 7 cases which were treated with this combination of CDDP with caffeine. Furthermore, a combination of 0.02 micrograms/ml CDDP (1/100 of peak plasma concentration) with 2 mM caffeine also showed more than 50% colony inhibition. Therefore, we assumed that caffeine was able to reduce the necessary dose of anti-tumor agent in some way. We stress that caffeine seems to be a very useful synergistic drug for causing lethality in sarcoma cells in combination with various DNA-damaging agents which are not effective on sarcoma cells.
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PMID:[A study of the effect of anti-tumor agents combined with caffeine on established lines of human osteosarcoma cells and primary cultured human sarcoma cells by clonogenic assay]. 347 41

Human osteosarcoma cells, that were cultured to confluence and maintained under low nutrient conditions, showed potentially lethal damage repair after cisplatin treatment. This repair was inhibited by a non-toxic dose of caffeine. Flow cytometric analysis indicated that cisplatin-treated cells accumulated in the S phase by 24 hr, followed by accumulation in the G2/M phase. Caffeine inhibited the initial accumulation in the S phase and the release of cells from the G2/M block. DNA synthesis was also inhibited by the cisplatin treatment. The addition of caffeine significantly reversed this inhibition. The content of DNA-bound platinum decreased over time after cisplatin treatment. Caffeine did not influence platinum content, nor did it directly affect the DNA excision repair. Cisplatin inhibits DNA synthesis in the S phase, but caffeine reduces this inhibition. Caffeine-treated cells that pass through S phase are incapable of recovery.
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PMID:Inhibitory effect of caffeine on potentially lethal damage repair in cisplatin-treated human osteosarcoma cells. 764 67

We treated three patients with osteosarcoma in extremity with intra-arterial combination chemotherapy using a regimen selected by succinate dehydrogenase inhibition chemosensitivity test, and used caffeine to enhance its effect. In two patients with osteosarcoma in distal diametaphysis of the radius and extraskeletal osteosarcoma in sole of the foot, the effect of intra-arterial combination chemotherapy was increased and followed by the functional limb salvage procedure. But in one patient with osteosarcoma in the proximal tibia, the effect of pre-operative intra-arterial combination chemotherapy could not be increased, so amputation was required. He was changed to a post-operative intra-venous combination chemotherapy regimen selected by chemosensitivity test of the surgical material. All patients have been continuously disease-free at five to twelve months after surgery.
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PMID:[Intra-arterial combination chemotherapy using both regimen selected by chemosensitivity test and caffeine to increase effect for osteosarcoma in extremity]. 794 68

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

Osteosarcoma is usually treated with intensive preoperative and postoperative chemotherapy and wide tumor resection, resulting in a 60% to 70% 5-year survival rate. Caffeine has a DNA-repair inhibiting effect. We therefore investigated the impact of caffeine given in conjunction with chemotherapy and limb-sparing surgery on survival and local tumor control in patients with nonmetastatic, high-grade osteosarcoma. Twenty-two patients were given 3 to 5 preoperative courses of intra-arterial cisplatin (120 mg/m2, 1 to 2 hours) and caffeine (1.5 g/m2/day x 3 days) with or without doxorubicin (30 mg/m2/day x 2 days). Following this treatment, limb-sparing surgery was performed by means of intentional marginal excision aiming at preservation of important structures such as major neurovascular bundles, tendons, ligaments and the epiphysis. Three courses of cisplatin and doxorubicin combined with caffeine, and high-dose methotrexate with vincristine and citrovorum factor rescue were given intravenously as postoperative chemotherapy for 21 patients and three courses of high-dose methotrexate and combination of ifosfamide, etoposide and methotrexate for 1 patient. Following the preoperative chemotherapy, there were no viable tumor cells in 19 patients, only scattered foci of viable cells in 2 patients, and some areas of viable tumor cells in 1. The 21 patients with a good chemotherapeutic response on radiographs underwent minimized marginal excision. Functional evaluation of the affected limbs was excellent for 17 patients, good for 3, fair for 1, and poor for 1. No local tumor recurrence was seen in this series. Eighteen patients remain disease-free with a mean follow-up of 61 months. Two patients died of metastatic disease, 1 died of chemotherapy-related complications, and 1 died of unknown causes. The overall 5-year cumulative survival rate was 90%, and the 5-year event-free survival rate was 75%. Chemotherapeutic caffeine enhanced tumor necrosis and improved the success rate of limb-sparing surgery using marginal procedure without any adverse impact on survival. The results of our limited clinical trial appear to justify further prospective, multicenter randomized trials of the benefits of caffeine combined with chemotherapy for nonmetastatic osteosarcoma and other malignant neoplasms.
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PMID:Caffeine-assisted chemotherapy and minimized tumor excision for nonmetastatic osteosarcoma. 958 49

The authors report on intentional marginal excision for osteosarcoma in conjunction with caffeine assisted chemotherapy for the purpose of preservation of good limb function. Twenty-seven patients with osteosarcoma (22 patients with Stage IIB and five with Stage IIIB) preoperatively were given three-to-five courses of intraarterial cisplatin and caffeine without or with doxorubicin. For 26 (96%) responders to the chemotherapy, limb salvage surgery was conducted by means of an intentional marginal procedure, which led to the preservation of important structures such as major neurovascular bundles, tendons, ligaments, muscles, and the epiphysis. Tumors were located in the distal femur in 11 patients, the proximal tibia in eight, the proximal fibula in four, the proximal humerus in two, and the proximal femur in one patient. The histologic response of these 26 patients to the preoperative chemotherapy showed no viable cells in 19 patients with Stage IIB osteosarcoma and only scattered foci of viable cells in two patients with Stage IIB and five patients with Stage IIIB osteosarcoma. As for reconstruction, distraction osteogenesis was performed in eight patients, allograft or autoclaved bone and prosthesis composite in four, autoclaved bone in two, osteochondral allograft in two, megaprosthesis in six, and resection alone in four patients. The average functional evaluation of the 26 patients was 91% of normal. Local tumor recurrence was seen in one patient, whereas 18 patients with Stage IIB osteosarcoma remain diseasefree with a mean followup of 61 months. Two patients with Stage IIB osteosarcoma and four patients with osteosarcoma Stage IIIB died of the disease. Intentional marginal excision for osteosarcoma in conjunction with caffeine assisted chemotherapy is advantageous because it results in the preservation of healthy important structures, with joint preservation possible in selected cases. This approach should help to improve the success rate of limb salvage surgery for osteosarcoma and to preserve the function of the affected limb.
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PMID:Marginal excision for osteosarcoma with caffeine assisted chemotherapy. 997 73

The present study was performed to investigate whether the introduction of a wild-type p53 gene into human osteosarcoma cells could alter the growth rate and enhance the cytocidal effect of cisplatin (CDDP) and the synergistic antitumor effect of caffeine. The lipofection method was used to transfect a wild-type p53 expression plasmid into the human osteosarcoma cell line, Saos2, which has both p53 alleles deleted. The transfected cells, Saos2/p53, had a reduced growth rate compared with the parental cell line. The colorimetric WST-1 assay demonstrated that Saos2/p53 cells were twice as sensitive to CDDP alone at a 50% inhibition concentration than the parental Saos2 cells. Caffeine significantly potentiated the cytocidal effect of CDDP in the Saos2/p53 cells. Furthermore, the TUNEL assay revealed that following treatment both with CDDP alone and with CDDP combined with caffeine, a higher percentage of the Saos2/p53 cells underwent apoptosis than did the parental Saos2 cells. Therefore the cytocidal effect of CDDP and the synergistic antitumor effect of caffeine are enhanced by the introduction of a wild-type p53 gene into a human osteosarcoma cell line null for p53. This raises the possibility that gene therapy using the p53 gene may prove efficatious for human osteosarcomas lacking p53 and which are resistant to standard chemotherapy.
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PMID:Sensitization and caffeine potentiation of cisplatin cytotoxicity resulting from introduction of wild-type p53 gene in human osteosarcoma. 1076 61


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