Therapy of human ovarian cancer xenografts with intraperitoneal liposome encapsulated muramyl-tripeptide phosphoethanolamine (MTP-PE) and recombinant GM-CSF

Malik, Sanjeev; Martin, Dave; Hart, Ian R.; Balkwill, Frances R.

doi:10.1038/bjc.1991.92

Cited by 16 publications

(9 citation statements)

References 16 publications

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“…Macrophages can be activated in vivo and in vitro by contact with micro-organisms or their products (e.g. LPS, muramyldipeptide) (Daemen et al, 1986(Daemen et al, , 1989Fidler, 1992), and also by macrophageactivating factors such as interferon-gamma and GM-CSF (Grabstein et al, 1986;Malik et al, 1991;Dileepan et al, 1995;Verstovsek et al, 1995). Activated macrophages recognize and destroy tumour cells without harming non-tumorigenic cells.…”

mentioning

confidence: 99%

Effect of intraperitoneally administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) on the cytotoxic potential of murine peritoneal cells

et al. 1998

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We studied the effect of recombinant murine granulocyte–macrophage colony-stimulating factor(rmGM-CSF) on the cytotoxic potential of murine peritoneal cells. Mice received rmGM-CSF intraperitoneally using different dosages and injection schemes. At different time points after the last injection, mice were sacrificed, peritoneal cells isolated and their tumour cytotoxicity was determined by a cytotoxicity assay using syngeneic [methyl- 3 H]thymidine-labelled colon carcinoma cells. Also, the cytotoxic response to a subsequent in vitro stimulation with lipopolysaccharide was determined. Upon daily injection of 6000–54 000 U rmGM-CSF over a 6-day period, the number of peritoneal cells increased over ten fold with the highest rmGM-CSF dose. Increases in cell numbers was mainly due to increases in macrophage numbers. Upon injection of three doses of 3000 U rmGM-CSF per day for 3 consecutive days, the number of macrophages remained elevated for minimally 6 days. Although the peritoneal cells from rmGM-CSF-treated mice were not activated to a tumoricidal state, they could be activated to high levels of cytotoxicity with an additional in vitro stimulation of lipopolysaccharide. Resident cells isolated from control mice could be activated only to low levels of tumour cytotoxicity with lipopolysaccharide. Tumour cytotoxicity strongly correlated with nitric oxide secretion. When inhibiting nitric oxide synthase, tumour cell lysis decreased. Thus, the expanded peritoneal cell population induced by multiple injections of rmGM-CSF has a strong tumour cytotoxic potential and might provide a favourable condition for immunotherapeutic treatment of peritoneal neoplasms. © 1999 Cancer Research Campaign

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Effect of intraperitoneally administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) on the cytotoxic potential of murine peritoneal cells

et al. 1998

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“…Oral, intraperitoneal and intravesical in mice, intranasal and intratracheal treatment in rats collectively activated macrophages and demonstrated antitumor effect [40][41][42][43][44][45][46]. Thus, it appears that MTP-PE is efficiently delivered to local macrophages and is active in several settings.…”

Section: L-mtp-pe Efficacy On the Prevention Of Lung Metastases: Precmentioning

confidence: 96%

Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases

Mori¹,

Ando²,

Heymann³

2008

Expert Review of Anticancer Therapy

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Osteosarcoma is the most common form of primary malignant bone tumor. The use of chemotherapy drugs with many side effects, including high-dose methotrexate, doxorubicin, cisplatin and ifosfamide, has greatly improved osteosarcoma survival compared with surgery alone. However, for 20 years, overall survival remained at a plateau of 60-70% in nonmetastatic disease and 20-30% in metastatic osteosarcoma owing to lung metastases. Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) is a new agent that improves overall osteosarcoma survival (chemotherapy without L-MTP-PE 70% versus with L-MTP-PE 78%; p = 0.03). L-MTP-PE offers additional benefit for osteosarcoma treatment in combination with chemotherapy, particularly ifosfamide-containing regimens. Clinical experience indicates that side effects such as fever are temporary and controlled or prevented with ibuprofen and/or acetoaminophen premedication; severe side effects are rare. Although surgery will remain the main approach for osteosarcoma treatment of lung metastases, L-MTP-PE combined with other modalities, including chemotherapy, appears to be of benefit in these patients as well.

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“…As a result of these initial successes, other agents (platins and vinca alkaloids) have entered preliminary clinical trials and new liposomal preparations of camptothecins (Koshkina et al 2000 ;Verschraegen et al 2000) and topoisomerase inhibitors (Colbern et al 1998b ;Emerson et al 2000) are under investigation. In addition to the delivery of conventional cytotoxic drugs, there exists the possibility of encapsulating other groups of compounds such as radiation sensitizers (Harrington et al 1998), cytokines (Konno et al 1991) and immunomodulators (Malik et al 1991) within liposomes. Such possibilities are likely to ensure that the ® eld of liposomal drug delivery will remain an active area of research for the foreseeable future.…”

Section: Discussionmentioning

confidence: 99%

Liposomally targeted cytotoxic drugs for the treatment of cancer

Harrington

Syrigos

Vile

2002

Journal of Pharmacy and Pharmacology

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Therapy of human ovarian cancer xenografts with intraperitoneal liposome encapsulated muramyl-tripeptide phosphoethanolamine (MTP-PE) and recombinant GM-CSF

Cited by 16 publications

References 16 publications

Effect of intraperitoneally administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) on the cytotoxic potential of murine peritoneal cells

Effect of intraperitoneally administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) on the cytotoxic potential of murine peritoneal cells

Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases

Liposomally targeted cytotoxic drugs for the treatment of cancer

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