Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 4-month-old male infant with Stage I rhabdoid tumor of the kidney at presentation subsequently developed pulmonary metastatic disease shortly after diagnosis and initiation of Vincristine and Actinomycin D chemotherapy. The patient was then treated with cis-platinum and Adriamycin. Within 28 days he achieved a complete remission which was maintained for 5 months. Subsequent recurrent pulmonary lesions failed to regress with radiotherapy and high-dose cyclophosphamide when used as single sequential agents. Further clinical trials with cis-platinum and Adriamycin seem warranted since prognosis with this tumor is poor and successful chemotherapy after metastatic dissemination has not been previously reported.
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PMID:Rhabdoid tumor of the kidney: complete remission induced by cis-platinum and adriamycin. 626 11

Actinomycin D was tested in an experimental preparation to determine its efficacy in the prevention of intravenous metastases. B16 melanoma cells were injected intravenously in syngeneic C57/BL6 mice. Two cell lines of the tumor, designated F1 and F10, with widely different metastatic potentials, were maintained in tissue culture and utilized for evaluation of pulmonary metastases. When actinomycin D was given intraperitoneally at doses of 0.05 and 0.075 mg/kg for 5 days, the number of pulmonary metastases was significantly decreased (P less than .001) in both the F1 and F10 cell lines. Although reduction did occur with a single dose, maximum reduction of pulmonary metastases was effected with a dose schedule administered over 5 days. Evaluation of a group of mice 2 and 3 wk after injection of tumor cells revealed that the effects of actinomycin D were not secondary to delay in tumor growth but did represent highly significant differences in numbers of metastatic lesions. It is concluded that in this experimental preparation actinomycin D, given in an adjuvant setting, can significantly reduce the number of pulmonary metastases. This study may have bearing on the design of adjuvant intraoperative and perioperative chemotherapy in order to destroy circulating tumor cells.
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PMID:Prevention of intravascular metastases of B16 murine melanoma: adjuvant chemotherapy with actinomycin D. 708 84

Because of the high incidence of pulmonary and skeletal metastases after only local treatment adjuvant systemic chemotherapy is mandatory in Ewing's sarcoma. The drugs most often used thereby are Actinomycin D, Cyclophosphamid, Anthracyclines and Vincristine. In polychemotherapeutic trials two year disease-free survival rates of 80% and more have been accomplished. The rate of local tumour control after radiotherapy is enhanced by chemotherapy but untoward reactions of bone and soft tissue are also. The extent of radiation portals and time indispensable dose of radiation therefore have to be reviewed again. But in view of debilitating side effects of radio-chemotherapy surgical procedures have to be considered individually.
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PMID:[On the chemotherapy of Ewing's sarcoma (author's transl)]. 726 93

182 patients with testicular tumors were treated since 1960. The best results from treatment of nonseminomatous germinative testicular tumors were obtained according to the following regimen: Stage A: (Tumor limited to the testis without invasion of the cord): Radical orchiectomy, lymphadenectomy, immune stimulation. Stage B1 (Invasion of the cord but less than 6 positive retroperitoneal lymph nodes): Additional triple chemotherapy with Actinomycin D, Chlorambucil and Methotrexate for 2 years. Stage B2 (More than 6 positive retroperitoneal lymph nodes): Additional radiotherapy with 4500 rads. Stage C (Distant metastases): Radical orchiectomy, retroperitoneal lymphadenectomy, immune stimulation, triple drug chemotherapy for 2 years with Actinomycin D, Methotrexate and Vincristine.
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PMID:[Treatment of testicular tumors]. 740 84

Thirty-seven patients with Ewing sarcoma were treated in the First National Chilean Trial for Ewing's Sarcoma (1986-1991), which comprised the St. Jude Ewing's 78 Study. All patients received cyclophosphamide, doxorubicin, vincristine, and Dactinomycin for a total treatment period of about 10 months, and all prescribed therapy was administered. Local therapy consisted of irradiation (RT) to the primary tumor, complete surgical resection, or a combination of both surgery and RT. Twenty-nine of these patients had localized tumors, 24% had pelvic primary tumors, 21 were males, and 20 were greater than 10 years of age at diagnosis. Twenty-one patients had tumors that were greater than 8 cm in largest diameter. Fourteen of the 29 patients with localized disease remain disease free at 23 to 91 months from diagnosis. Fourteen patients have died of-tumor-related complications and 1 of a secondary malignancy. Relapse was local only in 4, metastatic in 9, and local plus metastatic in 1. Only 1 of the 8 patients with metastatic disease at presentation remains disease free. Toxicity consisted primarily of myelosuppression and mucositis. We conclude that this form of relative intense multimodal therapy for children/adolescents with localized Ewing sarcoma is curative in about half of affected children as in the original St. Jude study, and that it can be safely given in a developing country, provided that careful attention to supportive care and treatment planning is given. Although these results represent improvement in outcome for our patients, more effective therapy is needed for children with Ewing sarcoma, especially those with metastatic disease at presentation.
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PMID:Multimodal therapy for children and adolescents with Ewing sarcoma: results of the First National Chilean Trial (1986-1991). 921 43

88 children with primary renal tumours (85 with nephroblastoma and 3 with renal cell carcinoma) were treated between 1973 and 1990 in the paediatric urology department of Institute "Pirogov" and the paediatric haematological oncology department in Sofia. Combined therapy includes early surgery (nephrectomy + lymphadenectomy) and combination chemotherapy (Dactinomycin, Vincristine + Adriamycin, Endoxan). Stage II (with lymph node in involvement), III and IV disease was treated by radiotherapy. Chemotherapy and preoperative radiotherapy were administered in the case of very large tumours. In this series of 88 children, 64 (72.2%) are alive and 21 (23.8%) have died, while no information was available for 3 cases (3.5%). Survival was related to clinical stage, histological type and the child's age. One of the 2 cases with bilateral tumours survived for more than 2 years after the operation and combined therapy. One girl with liver and spleen metastases survived in remission for 11 years after the operation. Two children with pulmonary metastases, discovered one year after surgery for the primary tumour survived in remission for 4 and 14 years, respectively. The authors discuss the good results obtained with early combined therapy in this type of tumour.
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PMID:[Late results of the complex treatment of primary kidney neoplasm in children]. 950 34

The carbohydrate antigen sialyl-Lewis(a) is important to pancreatic tumour biology because the circulating antigen is used in serological tests for malignancy and because cell surface antigen is involved in tumour cell binding to the endothelial adhesion molecule, E-selectin, in extravasation. In this study, we examined the effects of the adenylyl cyclase activator, forskolin, and the diacylglycerol analogue, phorbol 12-myristate 13-acetate (PMA), on the expression and release of sialyl-Lewis(a) in human pancreatic cancer cells. Increases in the release of sialyl-Lewis(a) from SW1990 cells produced by forskolin and PMA were associated with increases in the activities of protein kinases A and C, respectively, and could be blocked by inhibitors specific for these enzymes. Immunoprecipitation experiments showed that sialyl-Lewis(a) was associated with MUC1 mucin. Forskolin also increased the cellular content of antigen and MUC1 mRNA. Actinomycin D and a protein kinase A inhibitor, H8, blocked these effects. In contrast, PMA reduced cellular antigen and MUC1 mRNA levels, although it produced a temporary increase in release of the antigen. The effects of PMA were blocked by the protein kinase C inhibitor, H7. PMA also reduced cell binding to the adhesion molecule E-selectin. In summary, PKA and PKC alter cell MUC1-associated sialyl-Lewis(a) in opposite directions. These changes may have clinical utility in the diagnosis of pancreatic cancer and the prevention of metastases.
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PMID:Forskolin and phorbol ester have opposite effects on the expression of mucin-associated sialyl-Lewis(a) in pancreatic cancer cells. 1074 4

Previously we demonstrated that addition of Tumour Necrosis Factor-alpha to melphalan or doxorubicin in a so-called isolated limb perfusion results in synergistic antitumour responses of sarcomas in both animal models and patients. Yet, 20 to 30% of the treated tumours do not respond. Therefore agents that synergise with tumour necrosis factor alpha must be investigated. Actinomycin D is used in combination with melphalan in isolated limb perfusion in the treatment of patients with melanoma in-transit metastases and is well known to augment tumour cell sensitivity towards tumour necrosis factor alpha in vitro. Both agents are very toxic, which limits their systemic use. Their applicability may therefore be tested in the isolated limb perfusion setting, by which the tumours can be exposed to high concentrations in the absence of systemic exposure. To study the beneficial effect of the combination in vivo, BN-175 soft tissue sarcoma-bearing rats were perfused with various concentrations of actinomycin D and tumour necrosis factor alpha. When used alone the drugs had only little effect on the tumour. Only when actinomycin D and tumour necrosis factor alpha were combined a tumour response was achieved. However, these responses were accompanied by severe, dose limiting, local toxicity such as destruction of the muscle tissue and massive oedema. Our results show that isolated limb perfusion with actinomycin D in combination with tumour necrosis factor alpha leads to a synergistic anti-tumour response but also to idiosyncratic locoregional toxicity to the normal tissues. Actinomycin D, in combination with tumour necrosis factor alpha, should not be explored in the clinical setting because of this. The standard approach in the clinic remains isolated limb perfusion with tumour necrosis factor alpha in combination with melphalan.
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PMID:Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity. 1195 68

The prognosis of rhabdomyosarcoma (RMS) in advanced stages is still sobering. Therapy is limited due to local tumor recurrence, development of metastases and multidrug resistance. The aim of this study was to investigate the development of multidrug resistance in cell lines and in xenografts of alveolar and embryonal RMS treated according to the German Soft Tissue Sarcoma Study (CWS). Alveolar and embryonal RMS cell lines were treated with Vincristine, Topotecan, Carboplatin, Actinomycin D, or Ifosfamide. Expression levels of resistance-associated genes were assessed using Real time-PCR. Nude mice (NMRI nu/nu, n = 10 per group) underwent xenotransplantation of human embryonal or alveolar RMS. Animals were treated with standard chemotherapeutic drugs Vincristine, Topotecan, Carboplatin, Actinomycin D, or Ifosfamide according to treatment schedules of the CWS-study. Tumor sizes were measured and relative tumor volumes were calculated. Animals were sacrificed after 20 days and standard histology, Real-time-PCR for MDR1-, MRP-, LRP- and MDM2-gene as well as immunohistochemistry for MDR1-, LRP-, and MRP-protein were performed. In the cell lines, an up-regulation of MDR-1 gene was found in alveolar rhabdomyosarcoma. In embryonal rhabdomyosarcoma, an up-regulation of LRP and MRP was found. Standard chemotherapy of alveolar rhabdomyosarcoma resulted in a significant reduction of tumor growth (P < 0.05) in all groups. In embryonal rhabdomyosarcoma strongest effects were found after treatment with Ifosfamide, Vincristine and Carboplatin (P < 0.05). RT-PCR revealed a MDR1-dependent mechanism in alveolar rhabdomyosarcoma. In embryonal rhabdomyosarcoma, MDR1 occurred to a lower degree. Immunohistochemistry revealed correlating expression levels of multidrug resistance-associated proteins. The use of established chemotherapy on human RMS in vivo had strong effects on xenografts compared to their controls. In all cases, there was only a reduction of tumor growth, but not a complete eradication of the tumors. Chemotherapy seemed to upregulate the expression of resistance-associated genes in vitro and in vivo. The mechanism of multidrug resistance depends on the tumor subtype. Therefore, further investigations will be required to evaluate multidrug resistance in patients and to investigate new modalities for a reversal of multidrug resistance.
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PMID:Effects of standard chemotherapy on tumor growth and regulation of multidrug resistance genes and proteins in childhood rhabdomyosarcoma. 1721 91


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