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PubMed · 15816079

Beta testing.

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2005. Beta testing.. https://pubmed.ncbi.nlm.nih.gov/15816079/

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The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by beta-blockers.

The development of metastases is a decisive step in the course of a cancer disease. The detection of metastases in cancer patients is correlated with a poor prognosis, and over 90% of all deaths from cancer are not due to the primary tumor, which often can be successfully treated, but are due to the metastases. Tumor cell migration, a prerequisite for metastasis development, is not merely genetically determined, but is distinctly regulated by signal substances of the environment including chemokines and neurotransmitters. We have shown previously that the migration of breast, prostate, and colon carcinoma cells is enhanced by the stress-related neurotransmitter norepinephrine in vitro, and that this effect can be inhibited by the beta-blocker propranolol. We now provide for the first time evidence for the in vivo relevance of this neurotransmitter-driven regulation using PC-3 prostate carcinoma cells. The development of lumbar lymph node metastases in athymic BALB/c nude mice increased with the application of norepinephrine via microosmotic pumps, while propranolol inhibited this effect. However, the growth of the primary tumor was not affected by either treatment. Additionally, experiments using human tissue microarrays showed that 70-90 percent of breast, colon, and prostate carcinoma tissues express the relevant beta2-adrenoceptor. Thus, our work contributes to the understanding of the basic cellular mechanisms of metastasis development, and furthermore delivers a rationale for the chemopreventive use of clinically established beta-blockers for the inhibition of metastases.

Adrenergic beta-Antagonists↗

Does atrial fibrillation in very elderly patients with chronic systolic heart failure limit the use of carvedilol?

BACKGROUND AND AIMS: It is well known that beta-blockers are useful in patients with chronic heart failure (CHF). These favourable effects have recently been observed even in elderly CHF patients. Objectives of the present study were to evaluate the feasibility, tolerability and safety of carvedilol therapy in a cohort of patients > 70 years of age with CHF and left ventricular ejection fraction < 40% with chronic atrial fibrillation. For this purpose, we designed an observational, 12-month prospective study. RESULTS: Among 240 patients who were referred to our centers and met inclusion criteria, 64 had chronic atrial fibrillation (27%). Thirty-nine out of these 64 subjects (61%) were treated with carvedilol, while 25 patients (39%) had contraindications to such treatment. In the cohort of 176 patients with stable sinus rhythm (control group), carvedilol could be administered in 121 patients (69%), while it was not given in 55 (31%, p=ns). Airways disease was the main reason for exclusion from carvedilol in this setting of patients. No difference in 1-year tolerability of study drug was observed among patients with chronic atrial fibrillation (29 of 33 patients=87.9%) and stable sinus rhythm (95 of 102=93.1%). Adverse events leading to the discontinuation of carvedilol in these two populations were rare and never resulted in any disability, death or were life-threatening. CONCLUSION: In over-70 patients with systolic CHF, chronic atrial fibrillation does not limit the possibility of testing beta-blocker therapy. Carvedilol was equally tolerated and safe in patients with atrial fibrillation and sinus rhythm.

Adrenergic beta-Antagonists↗