The use of haemoregulatory peptides (pEEDCK monomer and dimer) for reduction of cytostatic drug induced haemopoietic damage

Paukovits, Walter R.; Moser, Marie-Hέlène; Binder, Konrad; Paukovits, Johanna B.

doi:10.1016/0305-7372(90)90068-q

Cited by 10 publications

(6 citation statements)

References 5 publications

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“…The results presented in this study generally agree with those reported by other groups using HP5b (Paukovits et al, 1990b) or other hematopoietic inhibitors, such as AcSDKP (Cashman et al, 1994), to prevent the myelosuppression associated with anti-cancer therapy. Short-term infusion or injection of HP5b was found to protect 50% of the animals from a lethal dose of Ara-C (Paukovits et al, 1991a).…”

Section: Discussionsupporting

confidence: 82%

“…The short duration would imply minimal adverse effects from rendering the bone marrow unresponsive. This approach, combined with the subsequent administration of agents stimulating hematopoiesis, has been shown (Paukovits et al, 1990b) to be effective in rapidly normalizing the peripheral blood cells in terms of number of cells, as well as the maturity of these cells, following short-term use of cytostatic drugs (Paukovits et al, 1991a).…”

mentioning

confidence: 99%

“…Reports from other laboratories (Paukovits et al, 1990a(Paukovits et al, , 1991Guigon and Bonnet, 1995) suggest that the latter strategy has been effective in reducing myelotoxicity associated with chemotherapy. Several agents that suppress hematopoiesis have been described, e.g., AS101 (Shani et al, 1990), Amifostine (WR-2721) (Shapall et al, 1994), arotinoid (Eliason et al, 1993), the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcS-DKP, Seraspenide) (Cashman et al, 1994) and the pentapeptide, pGlu-Glu-Asp-Cys-Lys (pEEDCK, HP5b) (Paukovits et al, 1990b). The naturally occurring peptides, AcSDKP and pEEDCK, have been well studied as inhibitors of myeloid-progenitor-cell differentiation and have been shown to protect against the toxic effects of chemotherapy.…”

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confidence: 99%

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Reduction in the duration of myelotoxicity associated with radioimmunotherapy with infusions of the hemoregulatory peptide, HP5b in mice

et al. 1997

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The hemoregulatory peptide, pGlu-Glu-Asp-Cys-Lys (pEEDCK or HP5b), has been shown to reversibly inhibit the proliferation of bone-marrow progenitor cells, and has been reported to protect mice from the myelotoxicity associated with ara-C, a chemotherapeutic agent. We undertook to use this reagent to reduce radioimmunotherapy(RAIT)-associated bone-marrow toxicity by suppressing hematopoiesis during the critical period when bone marrow is exposed to radiation. The reported studies optimize the use of HP5b to reduce the duration of neutropenia and thrombocytopenia. We found that 3.6 mg/day of HP5b administered through a continuous 7d mini-osmotic pump, together with a bolus dose of 3.6 mg 3 hours before the radioantibody dose, gave the best effect, as measured by neutrophil counts on day 28 post RAIT. With sub-lethal doses of RAIT, the period of neutropenia was reduced by 2 weeks, and there appeared to be more rapid recovery of morphologically mature myeloid cells. The peptide, however, does not appear to alleviate the lymphotoxicity associated with RAIT. No adverse effects have been noted from continuous infusions of the peptide. In the past, we reported that cytokines (IL-1/GM-CSF) are not marrowrestorative when given after RAIT. However, an additive effect is observed when HP5b infusions are combined with post-RAIT cytokine administration, suggesting that a significant pool of bone-marrow progeniter cells remains when HP5b is co-administered with RAIT. Thus, HP5b is an alternate approach to reducing myelotoxicity, and may be used in combination with cytokines to further reduce the duration of myelosuppression. Int.

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Section: Discussionsupporting

confidence: 82%

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confidence: 99%

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confidence: 99%

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Reduction in the duration of myelotoxicity associated with radioimmunotherapy with infusions of the hemoregulatory peptide, HP5b in mice

et al. 1997

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“…24 Pyro-EEDCK-like sequences have been identified in the G iα chains of GTP-binding proteins at position 63-67, proximal to the major phosphorylation site. 24,26 Oxidation of the cysteine thiol groups of pyro-EEDCK can lead to formation of a disulphide-bridged homodimer (pyro-EEDCK) 2 which, unlike the monomer, is a potent stimulator of hematopoiesis.…”

Section: Pepcat Analysis Of Pentapeptide Pyro-eedckmentioning

confidence: 99%

PEPCAT?A new tool for conformational analysis of peptides

et al. 2000

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“…This has been purified to homogeneity revealing the sequence pEEDCK (Paukovits & Laerum 1982). This peptide appears to act through a protease sensitive membrane receptor (Paukovits & Paukovits 1975) and is active in inhibiting murine and human myelomonocyticrestricted progenitor cells, the granulocyte/macrophage colony-forming cells (GM-CFC) as well as CFU-S and Long-term culture initiating cells (Paukovits et al 1990(Paukovits et al , 1991(Paukovits et al , 1993. Inhibitory activity is observed at 10-13 M however, the dose response is biphasic and inhibitory properties are lost at higher concentrations.…”

Section: Inhibitors Of Stem Cell Proliferationmentioning

confidence: 99%

Haemopoietic stem cells: their heterogeneity and regulation

Graham

Wright

1997

Int J Experimental Path

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Summary. The maintenance of the various blood cell populations in mammals is achieved by the proliferation and differentiation of precursor cells located primarily in the bone marrow. These precursor cells are all derived from a common haemopoietic stem cell population that is established during embryogenesis and functions for the lifetime of the organism. An overview is given of the various assay systems for haemopoietic stem cells, how these assays have contributed to understanding the considerable heterogeneity within the stem cell compartment, the regulation of stem cells and the development of the haemopoietic system.

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The use of haemoregulatory peptides (pEEDCK monomer and dimer) for reduction of cytostatic drug induced haemopoietic damage

Cited by 10 publications

References 5 publications

Reduction in the duration of myelotoxicity associated with radioimmunotherapy with infusions of the hemoregulatory peptide, HP5b in mice

Reduction in the duration of myelotoxicity associated with radioimmunotherapy with infusions of the hemoregulatory peptide, HP5b in mice

PEPCAT?A new tool for conformational analysis of peptides

Haemopoietic stem cells: their heterogeneity and regulation

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