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The effect of anesthetic technique on µ-opioid receptor expression and immune cell infiltration in breast cancer.

ABSTRACT: BACKGROUND:Clinical histological studies demonstrate that the distribution of natural killer (NK) cells, other immune cells and ?-opioid receptors (MOR) within cancer tissue can predict cancer prognosis. No clinical study has evaluated whether anesthetic technique influences immune cell and MOR expression within human breast cancer. METHODS:Excised preoperative biopsies and intraoperative breast cancer specimens from 20 patients randomly chosen from patients previously enrolled in an ongoing, prospective, randomized trial (NCT00418457) investigating the effect of anesthetic technique on long-term breast cancer outcome were immunohistochemically stained and microscopically examined by two independent investigators, masked to randomization, to quantify MOR and immune cell infiltration: CD56, CD57 (NK cells), CD4 (T helper cells), CD8 (cytotoxic T cells) and CD68 (macrophages). Patients had been randomized to receive either a propofol-paravertebral anesthetic with continuing analgesia (PPA, n?=?10) or balanced general anesthetic with opioid analgesia (GA, n?=?10). RESULTS:There were no differences between the groups in staining intensity in preoperative biopsy specimens. Expression intensity values (median 25-75%) for MOR in intraoperative resected biopsy were higher in GA 8.5 (3-17) versus PPA 1 (0-10), p?=?0.04. The numbers of MOR-positive cells were also higher in GA patients. Expression and absolute numbers of CD56, CD57, CD4 and CD68 were similar in resected tumor in both groups. CONCLUSION:General anesthesia with opioid analgesia increased resected tumor MOR expression compared with propofol-paravertebral anesthetic technique, but the anesthetic technique did not significantly influence the expression of immune cell markers.

SUBMITTER: Levins KJ

PROVIDER: S-EPMC6267716 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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The effect of anesthetic technique on µ-opioid receptor expression and immune cell infiltration in breast cancer.

Levins Kirk J KJ Prendeville S S Conlon S S Buggy D J DJ

Journal of anesthesia 20180918 6

<h4>Background</h4>Clinical histological studies demonstrate that the distribution of natural killer (NK) cells, other immune cells and μ-opioid receptors (MOR) within cancer tissue can predict cancer prognosis. No clinical study has evaluated whether anesthetic technique influences immune cell and MOR expression within human breast cancer.<h4>Methods</h4>Excised preoperative biopsies and intraoperative breast cancer specimens from 20 patients randomly chosen from patients previously enrolled in ...[more]

PMID: 30229370

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Project description:ObjectiveThe iboga alkaloids are a class of small molecules defined structurally on the basis of a common ibogamine skeleton, some of which modify opioid withdrawal and drug self-administration in humans and preclinical models. These compounds may represent an innovative approach to neurobiological investigation and development of addiction pharmacotherapy. In particular, the use of the prototypic iboga alkaloid ibogaine for opioid detoxification in humans raises the question of whether its effect is mediated by an opioid agonist action, or if it represents alternative and possibly novel mechanism of action. The aim of this study was to independently replicate and extend evidence regarding the activation of ?-opioid receptor (MOR)-related G proteins by iboga alkaloids.MethodsIbogaine, its major metabolite noribogaine, and 18-methoxycoronaridine (18-MC), a synthetic congener, were evaluated by agonist-stimulated guanosine-5´-O-(?-thio)-triphosphate ([(35)S]GTP?S) binding in cells overexpressing the recombinant MOR, in rat thalamic membranes, and autoradiography in rat brain slices.Results and significanceIn rat thalamic membranes ibogaine, noribogaine and 18-MC were MOR antagonists with functional Ke values ranging from 3 uM (ibogaine) to 13 uM (noribogaine and 18MC). Noribogaine and 18-MC did not stimulate [(35)S]GTP?S binding in Chinese hamster ovary cells expressing human or rat MORs, and had only limited partial agonist effects in human embryonic kidney cells expressing mouse MORs. Ibogaine did not did not stimulate [(35)S]GTP?S binding in any MOR expressing cells. Noribogaine did not stimulate [(35)S]GTP?S binding in brain slices using autoradiography. An MOR agonist action does not appear to account for the effect of these iboga alkaloids on opioid withdrawal. Taken together with existing evidence that their mechanism of action also differs from that of other non-opioids with clinical effects on opioid tolerance and withdrawal, these findings suggest a novel mechanism of action, and further justify the search for alternative targets of iboga alkaloids.

Dataset Information

The effect of anesthetic technique on µ-opioid receptor expression and immune cell infiltration in breast cancer.

Publications

The effect of anesthetic technique on µ-opioid receptor expression and immune cell infiltration in breast cancer.

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