Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis

Erin, Nuray; Duymuş, Özlem; Öztürk, Saffet; Demır, Necdet

doi:10.1016/j.regpep.2012.08.001

Cited by 47 publications

(38 citation statements)

References 45 publications

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“…However, two experimental studies in mice showed that vagotomy or capsaicin-induced denervation enhanced cancer metastasis (47,48), demonstrating experimentally the protective effects of the vagus nerve on cancer progression. Furthermore, a recent study found an anti-inflammatory drug that activates the vagus nerve (CNI-1493) to reduce tumor burden in a breast cancer murine model (49). Collectively, these results support the theory that this nerve plays a pivotal homeostatic role whose function may be disease prevention or protection against poor prognosis in certain types of cancer.…”

Section: Discussionmentioning

confidence: 52%

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

Couck¹,

Brummelen²,

Schallier³

et al. 2013

Oncology Reports

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Abstract. Recent studies suggest that vagal nerve activity, indexed by heart rate variability (HRV), could have a prognostic role in cancer. However, most studies did not control adequately for confounders and included cardiac patients. Furthermore, the validity of this prognostic role needs to be tested in different types of cancer. The present study tested the prognostic role of HRV in prostate cancer (PC) and non-small cell lung cancer (NSCLC) patients, using a historical prospective design. HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients. Outcomes included prostate-specific antigen (PSA) at 6 and 24 months in PC, and overall survival (OS) (for the full sample) and survival time (for the deceased patients) in NSCLC. Furthermore, the possible mediating role of C-reactive protein (CRP) was tested (in NSCLC), as well as whether age and stage moderated the relationship between HRV and prognosis in both types of cancer. In the PC patients, HRV significantly inversely predicted PSA levels at 6 and 24 months, independent of confounders. Furthermore, this was particularly significant in metastatic PC patients, indicating moderation by stage. In NSCLC patients, HRV did not predict OS and survival time, but it did positively predict survival time in patients under the age of 65, independent of confounders. Additionally, CRP was not found to mediate the relationship between HRV and OS or survival time in NSCLC. The present results partly support previous studies and extend them to two additional common types of cancer, using a more rigorous control over confounders. Together with recent experimental findings, these results propose a modulatory role of vagal nerve activity in cancer. Therefore, routine measurement of HRV in estimating prognosis in cancer may be considered.

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Section: Discussionmentioning

confidence: 52%

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

Couck¹,

Brummelen²,

Schallier³

et al. 2013

Oncology Reports

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show abstract

“…There is evidence for a potentially regulatory role of vagal activity in tumours. For instance, vagus nerve activation decreased breast cancer metastasis (Erin et al ., ) and vagal activity, reflected by heart rate variability, could also predict clinical prognosis in patients with non‐small‐cell lung cancer or prostate cancer, in a historical prospective design (De Couck et al ., ). Gidron et al .…”

Section: Present Challenges and Future Prospectsmentioning

confidence: 99%

Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases

Zhao

et al. 2015

British J Pharmacology

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Cardiovascular disease remains a major cause of disability and death worldwide. Autonomic imbalance, characterized by suppressed vagal (parasympathetic) activity and increased sympathetic activity, correlates with various pathological conditions, including heart failure, arrhythmia, ischaemia/reperfusion injury and hypertension. Conventionally, pharmacological interventions, such as β‐blocker treatment, have primarily targeted suppressing sympathetic over‐activation, while vagal modulation has always been neglected. Emerging evidence has documented the improvement of cardiac and vascular function mediated by the vagal nerve. Many investigators have tried to explore the effective ways to enhance vagal tone and normalize the autonomic nervous system. In this review, we attempt to give an overview of these therapeutic strategies, including direct vagal activation (electrical vagal stimulation, ACh administration and ACh receptor activation), pharmacological modulation (adenosine, cholinesterase inhibitors, statins) and exercise training. This overview provides valuable information for combination therapy, contributing to establishment of a comprehensive system on vagal modulation from the aspects of clinical application and lifestyle improvement. In addition, the mechanisms contributing to the benefits of enhancing vagal tone are diverse and have not yet been fully defined. We endeavour to outline the recent findings that advance our knowledge regarding the many favourable effects exerted by vagal activation: anti‐inflammatory pathways, modulation of NOS and NO signalling, regulation of redox state, improvement of mitochondrial biogenesis and function, and potential calcium regulation. This review may help to develop novel therapeutic strategies targeting enhancing vagal activity for the treatment of cardiovascular diseases. Linked Articles This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23

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“…34 Although the role of these molecules in other diseases was demonstrated previously, the possible contribution in AMI has not been studied. 35 The NPY is a 36-amino acid peptide neurotransmitter found in the brain and autonomic nervous system. It regulates energy usage, and is involved in learning, memory processing, and epilepsy.…”

Section: Resultsmentioning

confidence: 99%

Substance P and Neuropeptide Y as Potential Biomarkers for Diagnosis of Acute Myocardial Infarction in Korean Patients

Han¹,

Seo²,

Jung³

et al. 2014

Bulletin of the Korean Chemical Society

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Substance P and neuropeptide Y were discovered as early diagnostic biomarkers of acute myocardial infarction in Korean patients and confirmed using enzyme-linked immunosorbent assay (ELISA). We screened 12 peptides from the sera of Korean acute myocardial infarction (AMI) patients and detected 3 peptides (neuropeptide Y, substance P, and N-terminal pro-B-type natriuretic peptide) to be elevated from patients' sera by liquid chromatography mass/mass spectrometry. The elevated concentration of 3 peptides was confirmed by ELISA. The screening results revealed the substance P, neuropeptide Y, and pro-B-type natriuretic peptide (47-76) concentrations were higher in patients' sera than in healthy controls. The sensitivity and specificity of substance P for AMI diagnostic marker were 80% and 83%, respectively, and those of neuropeptide Y were 87% and 90%, respectively compared to healthy controls. These results suggest that substance P and neuropeptide Y could be used as early diagnostic biomarkers in patients with AMI.

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Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis

Cited by 47 publications

References 45 publications

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients

Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases

Substance P and Neuropeptide Y as Potential Biomarkers for Diagnosis of Acute Myocardial Infarction in Korean Patients

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