Phase I/II dose escalation study of angiotensin 1-7 [A(1-7)] administered before and after chemotherapy in patients with newly diagnosed breast cancer

Rodgers, Kathleen E.; Oliver, Jamie C.; diZerega, Gere S.

doi:10.1007/s00280-005-0078-4

Cited by 96 publications

(86 citation statements)

References 36 publications

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“…33 The pharmacologically developed drug Ang-1-7 is already in phase I/II clinical trials for the modulation of BM RAS in distinct disease states. 44,45 However, since most of the cellular effects of the local RAS are in an autocrine, paracrine and intracrine fashion, future drugs intended to modulate local RAS functions shall be prepared to have local targeted actions in the tissue microenvironment, such as inside BM.…”

Section: Discussionmentioning

confidence: 99%

Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders

Tatonyan

Sayitoğlu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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There is preliminary evidence that the local renin-angiotensin system (RAS) could affect neoplastic hematopoiesis. The aim of this study is to search messenger RNA (mRNA) expressions of the essential RAS elements in myeloid and lymphoid hematological neoplastic disorders. Forty-six patients with newly diagnosed myeloid (AML, biphenotypic leukemia, CML) or lymphoid (CLL, NHL, B-ALL, T-ALL) hematological disorders were included in the study. In the lymphoid group, the median expression values of RENIN, ACE1, ACE2 and ANGIOTENSINOGEN (ANGTS) mRNAs were 1.96%, 0.42%, 0.00% and 0.00%, respectively; in the myeloid group, 0.73%, 1.55%, 0.04% and 0.006%, respectively. In the lymphoid group, RENIN levels were significantly higher (p = 0.001), whereas ACE1 and ACE2 levels were significantly higher in the myeloid group (p values were 0.013 and 0.010, respectively). ANGTS levels were similar in both groups. In patients with non-ALL lymphoid malignancies, RENIN expressions were significantly higher when compared to ALL patients (p = 0.004). All patients with active disease had significantly higher RENIN mRNA expression levels than patients without active disease (2.03% vs 0.30%) (p = 0.034). The result of our present study indicates that the activities of local RAS may differ in distinct disease states such as leukemia and lymphomas.

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Section: Discussionmentioning

confidence: 99%

Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders

Tatonyan

Sayitoğlu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…14 However, research involving Ang-(1-7) is not restricted to cardiovascular and renal function. In recent years, investigations have demonstrated Ang-(1-7)-dependent effects on wound healing, 15 mechanisms involved in learning and memory, 16 cancer [17][18][19] and early progenitor cells. 20 Previously, we have shown that the receptor Mas is associated with Ang-(1-7)-stimulated intracellular signaling.…”

Section: Introductionmentioning

confidence: 99%

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

et al. 2012

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The renin-angiotensin system (RAS) has a vital role in regulating the cardiovascular system. The primary effector of the RAS is the octapeptide angiotensin (Ang) II, a potent regulator of blood pressure and water homeostasis. Ang II mediates its functions through the stimulation of two distinct receptors, AT 1 (two subtypes in rodents (AT 1a and AT 1b )) and AT 2 . It was shown that in addition to Ang II, shorter fragments of Ang are also biologically active. Ang-(1-7) came into focus because it opposes many of the detrimental effects of Ang II. However, it is still controversial whether Ang II receptors are involved in Ang-(1-7)-mediated signaling. To characterize the impacts of Ang II receptors on Ang-(1-7)-stimulated vascular relaxation, the effects of acute infusion of the three vasorelaxant compounds, that is, Ang-(1-7), bradykinin (BK) and acetylcholine (ACh), on heart rate (HR) and mean arterial pressure (MAP) were investigated in mice deficient for one, two or all three Ang II receptors. Ang-(1-7) and BK reduced MAP in wild-type, AT 1a /AT 1b -deficient and AT 2 -deficient mice. Although the change in absolute MAP values in the hypotensive triple knockouts (KO) could not be further reduced by both peptides, the percent change in MAP was comparable between the triple KO and wild-type mice. Both peptides did not alter the HR in all four genotypes. ACh significantly reduced absolute MAP values in all four genotypes with a similar percentage of reduction. In contrast to Ang-(1-7) and BK, ACh significantly reduced HR without genotypic differences. Our results generate proof that Ang-(1-7)-induced effects on MAP are mediated by a receptor that is independent of AT 1 and AT 2 .

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“…Likewise, Pantoja et al (2004) found that Ang-(1-7) exerted similar effects in breast cancer cells, possibly in part due to inhibition of angiogenesis. Indeed, Ang-(1-7) was examined in a Phase I/II clinical trial to determine its effectiveness and optimal dose against chemotherapy-induced cytopenias in breast cancer patients (Rodgers et al 2006). This study found that the heptapeptide attenuated cytopenias associated with chemotherapy without any hematologic toxicity.…”

Section: Ang-(1-7) and Growthmentioning

confidence: 99%

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

Trask

Ferrario

2007

Cardiovascular Drug Reviews

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Many advances have been made in the cardiovascular field in the last several decades. Among them is the progress completed to date on the heptapeptide member of the reninangiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)]. The peptide's beneficial actions against pathophysiological processes, such as cardiac arrhythmia, heart failure, hypertension, renal disease, preeclampsia, and even cancer are continuously being uncovered. This review encompasses the pharmacology of Ang-(1-7) and expounds upon the peptide's potential as a therapeutic agent against pathological processes both within and outside the cardiovascular continuum.

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Phase I/II dose escalation study of angiotensin 1-7 [A(1-7)] administered before and after chemotherapy in patients with newly diagnosed breast cancer

Abstract: These data suggest that A(1-7) may be beneficial in attenuating multilineage cytopenias following chemotherapy at a dose of 100 mug/kg per day.

Cited by 96 publications

References 36 publications

Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders

Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

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