Efecto de la endotelina-1 sobre las arterias tumorales de pacientes con neoplasia colorrectal

Herrero, Eduardo Ferrero; Villalón, A. L. García; Martínez, M. Labalde; Castrillo, G. Diéguez; Pascual, María Sancho

doi:10.4321/s1130-01082008000600003

Cited by 2 publications

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, prior reports showed that ET-1 is an important mediator of myogenic tone in isolated tumor arterioles and that tumor-feeding arterioles may be particularly sensitive to ET-1. 28,29 Thus, it was conceivable that elevated levels of ET-1 secreted locally by ET-1 cancer cells might lead to constriction of the adjacent vasculature to perturb blood flow to the tumor site. In support of this we made the following findings: (1) Treatment of mice with the vasodilator hydralazine led to a significant increase in the growth of ET-1 tumors, although it did not completely restore it to the level in the vector control; (2) Hydralazine treatment increased perfusion of ET-1 tumors; and (3) Vascular casts from ET-1 tumors showed constriction of afferent arterioles.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles

Weydert

Esser

Mejia

et al. 2009

Cancer Biology & Therapy

View full text Add to dashboard Cite

The vasoactive peptide endothelin-1 (ET-1) has been implicated in promoting the progression of prostate and other cancers though its precise mechanism(s)-of-action remain unclear. To better define the role of ET-1 in prostate cancer progression, we generated prostate cancer cell lines (PC-3 and 22Rv1) that express elevated levels of ET-1. As anticipated, increased ET-1 lead to modest autocrine growth stimulation of PC-3 cells in monolayer culture and increased colony formation in soft agar by both cell lines. Unexpectedly, however, metastatic colonization of 22Rv1 cells expressing elevated levels of ET-1 was reduced, as was the size of subcutaneous tumors produced by both 22Rv1- and PC-3 cells. Based on these data, we hypothesized that high levels of ET-1 may negatively impact the tumor microenvironment. We found that increased ET-1 expression did not consistently inhibit angiogenesis, indicating that this was not the cause of poor tumor growth. As an alternative explanation, we examined whether elevated ET-1 results in local vasoconstriction and thus reduces the blood supply available to the tumor. Consistent with this hypothesis, treatment of mice bearing PC-3 xenografts with a vasodilator increased tumor perfusion and partially restored tumor growth. Moreover, analysis of tumor vascular casts indicated vasoconstriction of tumor-feeding arterioles. Taken together, our data suggest that the local concentration of the ET-1 peptide is critical for determining a balance between its previously unrecognized tumor growth-suppressing activity (vasoconstriction) and known growth-promoting (mitogenesis, survival and angiogenesis) activities. These findings may have implications for the modification of current prostate cancer therapies involving ET-1.

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles

Weydert

Esser

Mejia

et al. 2009

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

Alteration of the renal regulatory hormonal pattern during experimental obstructive jaundice

Padillo

Cruz

Espejo

et al. 2009

Rev. esp. enferm. dig.

View full text Add to dashboard Cite

Objective: the alteration of hormones regulating sodium and water status is related to renal failure in obstructive jaundice (OJ).Experimental design: OJ was induced by common bile duct ligation. Samples were obtained from the control (SO) and OJ groups at 24 and 72 hours, and at 7 days. Different parameters related to biliary obstruction, liver and renal injury, and vasoactive mediators such as renin, aldosterone, endothelin-1 (ET-1) and prostaglandin E 2 (PGE 2 ) were studied.Results: bile duct ligation caused an increase in total bilirubin (p < 0.001) and alkaline phosphatase (AP) (p < 0.001). The SO and OJ groups had the same values for diuresis, renin, and creatinine clearance at 24 h. However, animals with OJ had a lower sodium concentration in urine than SO animals (p < 0.01), as well as an increase in aldosterone levels (p < 0.03). ANP levels were moderately increased during OJ but did not reach statistical significance when compared to the SO group. In contrast, OJ animals showed a rise in serum ET-1 concentration (p < 0.001) and increased PGE 2 in urine (p < 0.001).Conclusions: biliary obstruction induced an increase in ET-1 release and PGE 2 urine excretion. These hormones might play a role during the renal complications associated with renal disturbances that occur during OJ. INTRODUCTIONCholestasis is a clinical and biochemical syndrome caused by the impaired bile flow often associated with extrahepatic complications (1). Acute renal failure is a major complication of obstructive jaundice (OJ), with 8% incidence in several series (2). Biliary obstruction was first linked to renal failure in the early study carried out by Clairmont and von Haberer (1910) (3). Several hypotheses have sought to explain the pathogenesis of renal dysfunction in OJ. The depletion of the extracellular compartment (4), myocardial dysfunction, and altered hemodynamic status (5) have been linked to renal failure in biliary obstruction. In addition, severe oxidative stress has been implicated in the renal dysfunction associated to experimental OJ (6,7) as well as other liver diseases (8). Other lines of research have looked at the involvement of vasoactive mediators such as endothelin-1 (ET-1). ET-1 is a powerful paracrine vasoconstrictor that acts by means of specific type-A and type-B receptors. In biochemical terms, it is a 21-amino acid peptide derived from what is known as big ET-1 by the action of the endothelin-converter enzyme. It is synthesized mainly by endothelial cells and to a lesser degree by stellate cells in the liver and biliary epithelium (9,10). ET-1 changes have been related to different human diseases (11). ET-1 both acts on the mesangial cells and causes vasoconstriction in the renal microcirculation, which may contribute -along- Enferm Dig 2009; 101: 408-412.

show abstract

Efecto de la endotelina-1 sobre las arterias tumorales de pacientes con neoplasia colorrectal

Cited by 2 publications

References 14 publications

Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles

Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles

Alteration of the renal regulatory hormonal pattern during experimental obstructive jaundice

Contact Info

Product

Resources

About