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ACP is a process of behavior change with connections to the Transtheoretical Model of Behavior Change (TTM). This systematic review conducted a gap analysis of ACP interventions for clients with cancer by categorizing intervention components according to the TTM. PubMed, CINAHL Plus, MEDLINE, Cochrane Library, and Web of Science databases were searched for articles related to ACP and cancer. Intervention components were categorized using the TTM and outcomes evaluated.The search yielded 3,571 articles, with 20 meeting criteria. Most interventions were intended for the precontemplation and contemplation stages of change, with fewer intended for preparation, action, or maintenance. Multiple underutilized processes to engage ACP were identified. The majority of interventions were unsuccessful or neutral in engaging ACP. ACP interventions that are stage-matched, utilize diverse processes to engage ACP, address ACP as a process, and monitor engagement across the illness trajectory are needed.

Endothelin-1 (ET-1) is present at high concentrations in ovarian cancer ascites and is overexpressed in primary and metastatic ovarian carcinomas. In these tumours the presence of ET-1 is associated with enhanced neovascularization and with vascular endothelial growth factor (VEGF) expression. In these tumour cells, ET-1 acts as an autocrine growth factor selectively through the receptor ET A , which is predominantly expressed in tumour cells. Furthermore, ET-1 produced by ovarian tumour cells stimulates VEGF production and VEGF-mediated angiogenic effects through ET A binding. These results demonstrate that activation of the ET A in ovarian carcinoma cells promotes cell proliferation, neovascularization and invasion, which are the principal hallmarks of malignant transformation. The present study was designed to investigate the effects of the ET A -selective antagonist ABT-627 on the ET-1-induced mitogenic effect in both primary cultures (PMOV1 and PMOV2) and cell lines (OVCA 433 and HEY) of ovarian carcinoma. All tumour cells express the components of the ET-1 system and secrete ET-1. ET A blockade by ABT-627 inhibits ET-1- induced mitogenic effects. The ET B antagonist BQ-788 is ineffective although all cell lines express both ET A and ET B mRNAs. In conclusion, our results demonstrate that ABT-627 is capable of inhibiting the proliferative activity of ET-1, suggesting that this potent ET A antagonist may provide a novel approach to the multidisciplinary treatment of ovarian carcinoma.

The endothelin A receptor (ET(A)R) autocrine pathway is overexpressed in many malignancies, including ovarian carcinoma. In this tumor, engagement of ET(A)R triggers tumor growth, survival, neoangiogenesis, and invasion. To evaluate whether ET(A)R represents a new target in cancer treatment, we examine in vitro and in vivo the effect of the selective ET(A)R antagonist ABT-627 (atrasentan), a small p.o. bioavailable molecule, in mono- and combination therapy with taxane. ABT-627 effectively inhibits cell proliferation, vascular endothelial growth factor (VEGF) secretion of ovarian carcinoma cell lines, and primary cultures. ET(A)R blockade also results in the sensitization to paclitaxel-induced apoptosis. In ovarian carcinoma xenografts, in which the ET-1/ET(A)R autocrine pathway is overexpressed, tumor growth was significantly inhibited in ABT-627-treated mice compared with control. The therapeutic efficacy of ABT-627 was associated with a significant reduction in microvessel density, expression of VEGF, and matrix metalloproteinase-2, and increased the percentage of apoptotic tumor cells. Combined treatment of ABT-627 with paclitaxel produced additive antitumor, apoptotic, and antiangiogenic effects. These findings demonstrate that the small molecule ABT-627 is a candidate for clinical testing as an antitumor agent in ovarian cancer patients, especially in combination with taxane therapy. Interruption of ET(A)R signaling therefore, represents, a promising therapeutic strategy in ovarian carcinoma.

Endothelin-1 (ET-1) is present at high concentrations in ovarian cancer ascites and is overexpressed in primary and metastatic ovarian carcinoma. In these cells, ET-1 acts as an autocrine mitogenic and angiogenic factor selectively through the ET(A) receptor (ET(A)R). We investigated at mRNA and protein levels whether ET-1 could affect the expression and activation of metastasis-related proteinases and whether this process was associated with ovarian tumor cell invasion. ELISA, gelatin zymography, Western blot, and reverse transcription-PCR analyses demonstrated that in two ovarian carcinoma cell lines (HEY and OVCA 433), the expression of matrix metalloproteinase (MMP) -2, -9, -3, -7, and -13 was up-regulated and activated by ET-1. Moreover we observed that ET-1 was able to enhance the secretion and activation of membrane-type metalloproteinase-1, a critical mediator of invasiveness. The secretion of tissue inhibitor of metalloproteinase-1 and -2 was decreased by ET-1, which increased the net MMP/tissue inhibitor of metalloproteinase balance and the gelatinolytic capacity. In addition, ET-1 induced overexpression of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor type-1 and -2. Finally, we demonstrated that, in HEY and OVCA 433 cells, ET-1 dose-dependently increased migration and MMP-dependent invasion through Matrigel. BQ123, an antagonist of the ET(A)R, inhibited the ET-1-induced tumor protease activity and subsequent increase in cell migration and invasion. These findings demonstrate that ET-1 promotes ovarian carcinoma cell invasion, acting through the ET(A)R by up-regulating secretion and activation of multiple tumor proteinases. Therefore, ET-1 may represent a key component of more aggressive ligand-induced invasiveness of ovarian carcinoma.

In human papillomavirus (HPV)-positive cervical cancer cells, the en- dothelin A receptor (ETA R) mediates an endothelin-1-induced mitogenic effect, thus representing a relevant target for antitumor therapy. Here, we describe the complete inhibition of human cervix carcinoma growth by blocking the ETA R. In nude mice, the ETA R-selective antagonist atrasen- tan inhibits the growth and the neoangiogenesis of cervical carcinoma cell xenografts. Two cycles of treatment completely revert tumor growth. Atrasentan displays additive effects when administered in combination with the cytotoxic drug paclitaxel. These results demonstrate that by inhibiting cell proliferation and angiogenesis, this small molecule may help to control cervical cancer by either monotherapy or combination therapy.