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

Two cases of pleomorphic sarcoma with malignant fibrous histiocytoma phenotype that recurred following therapy with a distinctly different, more mature histologic appearance and immunohistochemical profile are reported. The first case recurred predominantly as extraosseous osteosarcoma at the same site 17 months after wide local excision. The second case recurred as widespread pulmonary, mediastinal, and hepatic metastatic disease 5 years after wide local excision and adjuvant local radiotherapy and chemotherapy with doxorubicin hydrochloride (Adriamycin) and cyclophosphamide (Cytoxan). Fine-needle aspiration of the pulmonary metastatic lesions showed predominantly spindle cells without any large, pleomorphic giant cells typical of malignant fibrous histiocytoma. The patient was treated by radiotherapy to the lung and mediastinum and by chemotherapy with ifosfamide and mesna. Biopsy of a metastatic scrotal skin nodule 9 months later showed a malignant spindle cell lesion with the histologic appearance and immunohistochemical phenotype of leiomyosarcoma. Retrospective immunohistochemical evaluation of the primary tumor showed focal desmin expression, suggesting focal leiomyosarcomatous differentiation. However, the large proportion of the primary tumor had the phenotype of malignant fibrous histiocytoma. These two cases illustrate an unusual finding of "differentiation" rather than "dedifferentiation" in a recurrent sarcoma. The transformation to osteosarcoma and differentiated leiomyosarcoma demonstrates the potential for phenotypic changes in soft-tissue sarcomas and suggests that the malignant fibrous histiocytoma phenotype and more-differentiated sarcomas such as extraosseous osteosarcoma or leiomyosarcoma are related in a common pathway in differentiation from a primitive mesenchymal stem cell.
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PMID:Malignant fibrous histiocytoma phenotype in pleomorphic sarcoma differentiation in recurrent disease. 784 56

The tumourigenicity of the LNCaP prostatic cell line was investigated in vivo after prostatic (orthotopic), subcutaneous (ectopic) and concomitant implantations in male Balb/c nude mice. Swollen lymph nodes were detected in the inguinal region only after subcutaneous implantation but could not be characterized by immunohistochemistry. However, when grafted to Endoxan-pretreated mice, they generated well differentiated tumours which secreted prostate-specific acid phosphatase. A parallel study was conducted to investigate the metastatic potential of the LNCaP tumour using several routes of implantation (intravenous, bone contact, intrasplenic and intracranial). Tumours grew only after intracranial implantation. No production of either haematogenous or bony metastases was recorded.
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PMID:Unusual behaviour of the LNCaP prostate tumour xenografted in nude mice. 836 68

The efficacy of combination therapy including an oral gelatinase inhibitor (CT1746) and cytotoxic agent was analyzed using the murine Lewis lung carcinoma model. Primary tumors, pulmonary metastases, and sera from tumor-bearing animals had increased gelatinase B activity that was inhibited by CT1746 levels achievable in vivo. The combination of CT1746 and cyclophosphamide (CTX) was significantly more effective than either single agent in delaying local tumor growth (CT1746/CTX, 30.9 +/- 1.7 days; CT1746, 2.6 +/- 0.3 days; CTX, 19.5 +/- 1.1 days; P < .001) and reducing the number and size of pulmonary metastases [CT1746/CTX, 5 +/- 2 (15% metastases > 3 mm); CT1746, 15 +/- 4 (55% > 3 mm); CTX, 11 +/- 3 (63% > 3 mm); no treatment, 24 +/- 5 (62% > 3 mm); P < .001]. These data support the notion of combining matrix metalloproteinase inhibitors and cytotoxic agents to treat certain epithelial malignancies.
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PMID:Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma. 863 Oct 1

From January 1988 to October 1991, one hundred and twelve patients with non metastatic Ewing's sarcoma of bone were treated with a 6 drugs neoadjuvant chemotherapy protocol (IOR/Ew2) in which, to the four drugs usually used in the treatment of this tumor (vincristine, adriamycin, cyclophosphamide and dactinomycin), Ifosfamide and VP-16 were added. The local treatment consisted of radiation therapy in 52 cases, a surgical treatment was performed in 27 cases and in the remaining 33 cases both the previous treatments were used. At a mean follow-up of 4.5 years (3-6.5), 62 patients (55.3%) remained continuously free of disease and 50 relapsed: 41 with metastases, 8 with mestastases and local recurrence and 1 with local recurrence alone. These results do not differ from the ones obtained in our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol (IOR/Ew1) in which only VCR, ADM, CTX and actD were used (3 year CDFS: IOR/Ew2 = 60.7%-IOR/Ew1 = 55.1%). In IOR/Ew2 a higher DFS rate was observed in the patients with tumor located in the axile bones in comparison with that obtained in the previous study (IOR/Ew2 = 48.6%, IOR Ew1 = 25.6%). Despite the fact that these results came from a not-randomized study, the authors conclude that the addition of Ifosfamide and VP-16 to the four drugs standard regimen do not improve the outcome of patients with Ewing's sarcoma of bone, with the possible exception of the patients with tumor located in the axile bones. This data should be confirmed in further and larger studies.
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PMID:[Neoadjuvant treatment of Ewing's sarcoma: results obtained in 122 patients treated with a 6-drug chemotherapeutic protocol (vincristine, adriamycin, cyclophosphamide, dactinomycin, ifosfamide and etoposide)]. 868 41

The phase I trial in breast cancer conducted by Peters et al. defined a regimen of high-dose chemotherapy consisting of cyclophosphamide, cisplatinum and BCNU (CPA/cDDP/BCNU). In chemotherapy-resistant metastatic disease, 23% of patients achieved complete remission followed by early relapse. In a phase II study, 53% of stage IV patients with no prior treatment achieved complete response (CR) with 16% progression-free at five to nine years post-transplant. Chemically debulking with an Adriamycin, 5FU, and Methotrexate regimen (AFM) to minimal tumor burden achieved 68% CR, with approximately 20% disease-free patients at 36 months. Other high dose chemotherapy regimens have been developed, again demonstrating in stage IV patients complete remissions in excess of 65% and progression-free survival rates of 20-30%.
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PMID:Positive selection and ex vivo expansion of hematopoietic progenitors as autografts for high-dose chemotherapy, potential importance in patients with bone metastases. 885 28

When administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line therapy for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and an Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles (6 months) or standard treatment with oral cyclophosphamide (Cytoxan) 100 mg/m2/d days 1 through 14, intravenous methotrexate 40 mg/ m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisolone 40 mg/m2/d (CMFP) days 1 through 14 for six cycles (6 months). Patients whose disease progressed or relapsed were recommended to receive second-line epirubicin. Accrual has been completed with 208 patients randomized, but a preplanned interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by a linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months for paclitaxel-treated patients and 6.4 months for those given CMFP, with median survival durations of 17.3 and 11.3 months, respectively. Grades 3 and 4 neutropenia occurred in 64% of patients treated with paclitaxel and in 63% treated with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% of CMFP courses. Nine percent of the patients had major infections with CMFP, but none were seen with paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel-treated and 27% of CMFP-treated patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results on paclitaxel treatment as compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides comparable control of metastatic cancer to CMFP combination therapy when used as front-line treatment.
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PMID:Paclitaxel as first-line treatment for metastatic breast cancer. The Taxol Investigational Trials Group, Australia and New Zealand. 914 86

Breast cancer is the commonest malignancy in women and although identification of this multi-system disease has increased, the survival rates have not dramatically altered over the past four decades. Optimium treatment of patients with breast cancer is a subject of great debate and traditionally may be divided into surgery, radiotherapy, chemotherapy and hormone manipulation. Halsted's radical mastectomy, although initially superseded by more mutilating surgery involving removal of tumour, breast, pectoral muscles and axillary contents, has given way to more conservative surgery and breast conservation, so now removal of the tumour with a marginal of healthy tissue is possible. Additional loco-regional radiotherapy has added to the increasing number of treatment options available to both doctor and patient. Systemic adjuvant therapy, primarily hormonal therapy, is used with the aim of decreasing the incidence of recurrence and distant tumour development. Through the process of randomized controlled trials these new therapeutic treatments have shown to be effective in the treatment of locoregional disease. Surgery in patients with advanced systemic disease is limited, however radiotherapy is of considerable importance and can be used to treat or palliate sites of metastases. In recent years trials have assessed chemotherapeutic regimens. However, limited number of patients and adequate randomization have hindered the confident acceptance of these results. Cyclophosphamide, methotrexate and 5 fluorouracil still remain the standard chemotherapeutic regimen, however many new drugs are currently undergoing trials and these or combinations of these may prove to be of future clinical use. Dramatic advances in cell and molecular biology have allowed the development of novel breast cancer therapies. Specific oncogenes and loss of tumour suppressor genes have been associated with decrease patient survival, with the presence of lymph node metastases and with decreased relapse free survival. Growth factor receptor blockers and tyrosine kinase inhibitors may be developed to specifically eradicate breast cancer cells. Immunotherapy and gene therapy may produce effective therapies. Trials utilizing cytokines and trials increasing the immunogenicity of tumours have already reported promising results. Surgery, chemotherapy, radiotherapy and hormone manipulation are the major treatment arms of breast cancer therapy. However, breast cancer still accounts for 20 percent of all female cancer deaths and the overall survival of patients has remained relatively static over the past forty years. From our increasing understanding of the pathological processes involved in the development and spread of breast cancer, new pharmaceutical, immunological and gene therapies may dramatically increase the cure rate of this serious disease.
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PMID:The increasing efficacy of breast cancer treatment. 936 31

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

A 64-year-old was diagnosed with a stage 1aII clear cell adenocarcinoma of the ovary in 1986. Initial chemotherapy was with Cisplatinum, Cytoxan, and Adriamycin. A pelvic recurrence developed in 1991 which failed to respond to Carboplatin therapy, and progression of disease with retroperitoneal nodal and choroidal metastases was noted in 1992. Debulking of retroperitoneal disease along with radiotherapy and seventeen cycles of Taxol chemotherapy resulted in a sustained clinical remission for three years until December 1995 when a right pelvic recurrence was noted. The patient underwent resection of disease again and was restarted on Taxol which was continued for six cycles until increasing serum CA-125 and recurrent pelvic disease were noted.
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PMID:Ovarian epithelial carcinoma metastatic to the choroid of the eye: prolonged survival with radiation and taxol chemotherapy. 974 22

During the past year there have been a number of important advances in the area of systemic therapy for breast cancer. Combined chemoendocrine therapy has been shown to be more effective than tamoxifen alone in the adjuvant therapy of node-negative estrogen receptor-positive breast cancer. Preliminary results of a randomized trial suggest that the addition of paclitaxel to adjuvant AC (Adriamycin and Cytoxan) improves survival in patients with operable node-positive disease. In the treatment of metastatic disease, preliminary results of a randomized trial have shown docetaxel to be superior to doxorubicin in response rate. In hormonal therapy, third generation aromatase inhibitors have replaced megestrol acetate as second-line hormonal therapy in receptor-positive disease. There are promising recent data about anti-HER-2 antibody therapy and other new approaches. This article reviews these and other recent advances in the systemic therapy of breast cancer.
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PMID:Recent advances in systemic therapy for breast cancer. 981 30


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