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)

Spontaneous canine oral melanoma (COM) is a highly metastatic cancer, resistant to chemotherapy, and can serve as a model for cancer immunotherapy. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) can activate the tumoricidal activity of the monocyte-macrophage system following i.v. injection. The objective of these studies was to evaluate the therapeutic effectiveness of L-MTP-PE administered alone and combined with recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) in dogs undergoing surgery for oral melanoma. Ninety-eight dogs with histologically confirmed, clinically staged, oral melanoma were entered into two randomized, double-blind, surgical adjuvant trials. In trial 1, 50 dogs were stratified based on clinical stage and randomized to once a week L-MTP-PE or lipid equivalent (control). When all of the clinical stages were combined, no difference in disease-free survival or in survival time (ST) were detected. However, within stage I, dogs receiving L-MTP-PE had a significant increase in ST compared with control, with 80% of the dogs treated with L-MTP-PE still alive at >2 years. Within each stage II and stage III, there was no difference detected between the treatment groups. In trial 2, 48 dogs were stratified on the basis of clinical stage and extent of surgery (simple resection or radical excision), treated with L-MTP-PE two times a week, and randomized to rcGM-CSF or saline (placebo) given s.c. daily for 9 weeks. Within each stage and when all of the stages were combined, there was no difference between the treatment groups. In both studies, stage I COM is associated with a better prognosis. No effect on survival was observed with regard to tumor location in the oral cavity, sex, type/extent of surgery, or age. In a subset of dogs tested, pulmonary alveolar macrophage cytotoxicity was enhanced with combined rcGM-CSF and L-MTP-PE but not in dogs treated with L-MTP-PE alone. The present study indicates that after surgery, L-MTP-PE administered alone or combined with rcGM-CSF showed no significant antitumor activity in treating advanced stage COM. In early stage COM, L-MTP-PE was shown to result in a prolongation of ST. Furthermore, this study provides additional rationale for the use of the dog model for human malignant melanoma.
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PMID:Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl tripeptide, and granulocyte macrophage colony-stimulating factor. 1063 67

The combination of chemotherapy with immunotherapy may offer an advantage over either therapy alone and provide a greater potential for total tumor eradication. Monocyte/macrophage-mediated tumor cell killing is a major mechanism of the host's defense against primary and/or metastatic neoplasia. We evaluated the tumoricidal activity against canine osteosarcoma cells of canine pulmonary alveolar macrophages (PAM) exposed in vitro to two recombinant canine (rc) cytokines (rcTNF alpha and rcIFN gamma). We also evaluated the in vivo tumoricidal activity of PAM from dogs treated with the macrophage activator, liposome-encapsulated muramyl tripeptide-phosphatidyl-ethanolamine (L-MTP-PE) alone or in combination with doxorubicin (DOX). This study demonstrated that rcTNF alpha and rcIFN gamma significantly enhance in vitro canine PAM cytotoxicity against canine osteosarcoma cells, and that PAM from dogs treated with DOX + L-MTP-PE have enhanced cytotoxic activity against osteosarcoma cells when compared to dogs treated with DOX or L-MTP-PE alone. These findings support the rationale for combining a chemotherapy agent with an immunotherapy agent for the treatment of metastatic disease, and suggest a role for TNF alpha and IFN gamma as agents for stimulating the antitumor activity of macrophages.
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PMID:In vitro and in vivo enhancement of canine pulmonary alveolar macrophage cytotoxic activity against canine osteosarcoma cells. 1085 Feb 95

Liposome-encapsulated muramyl tripeptide-phosphatidyl ethanolamine (L-MTP-PE) was used in a pilot study for resectable melanoma patients who were at high risk for relapse. We entered 18 evaluable patients. The patient group included: (a) patients with stage III disease and clinically measurable regional metastases at presentation as confirmed by needle biopsy and (b) patients with stage IV disease presenting with measurable and resectable distant metastases confirmed by needle biopsy and limited to lungs, lymph nodes and subcutaneous tissues. L-MTP-PE was given for 4 weeks prior to surgical resection and for an additional 20 weeks postoperatively. Disease-free intervals were then determined based on the date of surgery. A preliminary report published in 1993 indicated an average disease-free interval of 18 months (range 8-33 months). This article presents an updated report on the long-term, disease-free survival status of these patients and shows that of the 18 evaluable patients, 4 remain free of disease for more than 5 years after surgical resection and therapy. The period of survival for these patients ranged from 69 months to more than 91 months (average 80.5 months). Although this was only a pilot study, we believe that the duration of survival indicates that L-MTP-PE may produce significant biologic activity in patients with melanoma, resulting in long-term benefits in terms of tumor eradication.
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PMID:Liposomal muramyl tripeptide (CGP 19835A lipid) therapy for resectable melanoma in patients who were at high risk for relapse: an update. 1085 26

Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) is a synthetic biological investigational agent used for treating osteosarcoma. It has been used in both canine and human osteosarcoma to reduce pulmonary metastases, the most common pattern of treatment failure for sarcomas. L-MTP-PE has been well tolerated using the concept of biological cancer therapy during chemotherapy. The use of L-MTP-PE with ifosfamide is the best studied combination with single agent chemotherapy. This may represent a new treatment choice for osteosarcoma patients receiving ifosfamide. Such patients include those with a poor initial histological response to primary therapy and/or metastatic disease including pulmonary metastases. Reduction of side effects of L-MTP-PE, such as fever and/or flu-like symptoms, with ibuprofen has not reduced efficacy. Since improved symptom control is possible using drug combinations that are especially effective for delayed nausea, outpatient high-dose ifosfamide chemotherapy combined with L-MTP-PE may lead to a safe and effective therapy while maintaining the patients' quality of life.
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PMID:Liposomal muramyl tripeptide phosphatidyl ethanolamine: ifosfamide-containing chemotherapy in osteosarcoma. 1678 12

A new murine cell line, named GFPneu, was established from a mammary adenocarcinoma arising in double transgenic MMTVneu x CMV-GFP mice. Breast tumours develop in 100% of females after 2 months latency, as a result of the over-expression of the activated rat neu oncogene in the mammary glands. All tissues, and in particular the breast tumours, express the GFP protein. This cell line was tumorigenic when inoculated into nude mice and the derived tumours showed the same histological features as the primaries from which they were isolated. Their histopathology reproduces many characteristics of human breast adenocarcinomas, in particular their ability to metastasize. The GFP marker allows us to visualize the presence of lung metastases in fresh tissues immediately, to confirm the histopathology. From a lung metastatic fluorescent nodule, we derived a further cell line, named MTP-GFP, which we also characterized. These two cell lines could be useful to study the role played by the neu oncogene in the maintenance of the transformed phenotype, in the metastatic process, to test novel therapeutic strategies to inhibit primary tumour growth and to observe the generation of distant metastases.
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PMID:Establishment and characterization of new mammary adenocarcinoma cell lines derived from double transgenic mice expressing GFP and neu oncogene. 1710 43

The RECK (reversion-inducing cysteine rich protein with Kazal motifs) protein was initially discovered by its ability to induce reversion in ras-activated fibroblasts. The key action of RECK is to inhibit matrix metalloproteinases (MMPs) involved in breakdown of the extracellular matrix (ECM), and angiogenesis-namely MMP-2, MMP-9 and MTP-1. To this effect, it plays important physiological roles in embryogenesis and vasculogenesis. Additionally, it has a significant effect on tumorigenesis by limiting angiogenesis and invasion of tumours through the ECM. RECK has been studied in the context of a number of human tumours including colorectal, breast, pancreas, gastric, hepatocellular, prostate, and non-small cell lung carcinoma. In many of these tumours, RECK is down-regulated most likely as a result of inhibition at the Sp1 promoter site. MMP-2 and MMP-9 generally show an inverse association with RECK expression, but there are exceptions to this rule. Likewise, a reduction in tumour microvascular density (MVD) and VEGF have also been correlated with increased RECK levels, although more studies are required to define this effect. The predominant finding across all human tumour studies is a significantly improved prognosis (due to decreased invasion and metastasis) in tumours with preserved RECK expression. Although further research is required, RECK is a promising prognostic marker and potential therapeutic agent in multiple cancers.
Cancer Metastasis Rev 2007 Dec
PMID:RECK--a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer. 1782 69

Purpose. Original articles and abstracts published between January 1991 and January 1997 were selected according to specified criteria and reviewed to provide answers to five interesting questions about the systemic treatment of metastatic osteosarcoma.Results.(1) In patients with metastatic disease at presentation, what is the outcome after intensive multi-agent chemotherapy?Historically, survival has been poor, but may be improving with the use of ifosfamide-containing regimens.(2) Can response to new agents be evaluated better in patients who have received no previous chemotherapy?Based on limited data, this is probably true.(3) Is the response to neo-adjuvant chemotherapy, as determined by histopathology, similar for the primary tumor and synchronous pulmonary metastases?With intensive multi-agent chemotherapy, good histological response rates are in the range 70-90% for both groups.(4) What is the outcome, after intensive combined modality treatment with chemotherapy and surgery, in patients relapsing with metastases after previous adjuvant chemotherapy, and what are the important prognostic factors?Outcome is highly variable, but 5-year survival ranges between 25 and 50% and a good outcome is more likely if recurrent disease is limited to resectable lung metastases.(5) Can a biological agent (L-MTP-PE) prolong the time to relapse in patients with resected metastatic osteosarcoma?Preliminary data suggest that this is possible, but more studies are required.
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PMID:Metastatic osteosarcoma: a review of current issues in systemic treatment. 1852 Dec 13

The transmembrane domains (TMD) in membrane receptors play a key role in cell signaling. As previously shown by us a peptide targeting the TMD of neuropilin-1 (MTP-NRP1), blocks cell proliferation, cell migration and angiogenesis in vitro, and decreases glioblastoma growth in vivo. We now explored the clinical potential of MTP-NRP1 on breast cancer models and demonstrate that MTP-NRP1 blocks proliferation of several breast cancer lines including the MDA-MB-231, a triple negative human breast cancer cell line. In models with long term in vivo administration of the peptide, MTP-NRP1 not only reduced tumor volume but also decreased number and size of breast cancer metastases. Strikingly, treating mice before tumors developed protected from metastasis establishment/formation. Overall, our results report that targeting the TMD of NRP1 in breast cancer is a potent new strategy to fight against breast cancer and related metastasis.
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PMID:Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide. 2735 Nov 29

Cutaneous melanoma can metastasize to any organ, including brain and spinal cord. A 27-year-old lady, four months after conception presented with generalized seizures and was diagnosed to have subarachnoid hemorrhage. Further investigation did not reveal aneurysm. She underwent right ventriculo-peritoneal shunt for hydrocephalus and MTP for unprotected radiation from CT scan. Six weeks later she came to our institution with symptoms of dorsal compression. Imaging showed multiple intradural extramedullary spinal lesions at D3-D4, D8 and D10-D11. Surgical excision of the lesions was done and histopathology was consistent with metastatic deposits from malignant melanoma which was confirmed by immunohistochemistry studies also. Her conscious level deteriorated on the second postoperative day and CT scan showed multiple small tumor emboli with evidence of right temporal bleed and diffuse cerebral edema. In spite of aggressive treatment she could not be saved. This reported case concludes that pregnancy aggravates the clinical course of metastatic melanoma.
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PMID:Malignant Course of a Metastatic Melanoma During Pregnancy: A Case Report. 2914 29

The recruitment of autologous macrophages to attack osteosarcoma represents a novel immunotherapy approach to the treatment of osteosarcoma. Muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE) was derived as a compound with the ability to stimulate macrophages to destroy autologous osteosarcoma tumor cells. Preclinical studies including studies in dogs with spontaneously arising osteosarcoma showed the ability of L-MTP-PE to control microscopic metastatic disease in osteosarcoma. A pivotal clinical trial led to the approval of L-MTP-PE for the treatment of newly diagnosed osteosarcoma in over 40 countries.
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PMID:Muramyl Tripeptide-Phosphatidyl Ethanolamine Encapsulated in Liposomes (L-MTP-PE) in the Treatment of Osteosarcoma. 3248 36


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