Dataset Information

Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers.

ABSTRACT: BACKGROUND:Perioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an ?2-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite effects on primary tumour progression. We tested the effects of dexmedetomidine in clinically relevant models of dexmedetomidine use on cancer metastatic progression. METHODS:Dexmedetomidine was given to induce sub-hypnotic to sedative effects for 6-12 h, and its effects on metastasis formation, using various cancer types, were studied in naïve animals and in the context of stress and surgery. RESULTS:Dexmedetomidine increased tumour-cell retention and growth of metastases of a mammary adenocarcinoma (MADB 106) in F344 rats, Lewis lung carcinoma (3LL) in C57BL/6 mice, and colon adenocarcinoma (CT26) in BALB/c mice. The metastatic burden increased in both sexes and in all organs tested, including lung, liver, and kidney, as well as in brain employing a novel external carotid-artery inoculation approach. These effects were mediated through ?2-adrenergic, but not ?1-adrenergic, receptors. Low sub-hypnotic doses of dexmedetomidine were moderately beneficial in attenuating the deleterious effects of one stress paradigm, but not of the surgery or other stressors. CONCLUSIONS:The findings call for mechanistic translational studies to understand these deleterious effects of dexmedetomidine, and warrant prospective clinical trials to assess the impact of perioperative dexmedetomidine use on outcomes in cancer patients.

SUBMITTER: Lavon H

PROVIDER: S-EPMC6246773 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers.

Lavon H H Matzner P P Benbenishty A A Sorski L L Rossene E E Haldar R R Elbaz E E Cata J P JP Gottumukkala V V Ben-Eliyahu S S

British journal of anaesthesia 20171123 1

<h4>Background</h4>Perioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an α<sub>2</sub>-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite effects on primary tumour progression. We tested the effects of dexmedetomidine in clinically relevant models of dexmedetomidine use ...[more]

PMID: 29397129

Similar Datasets

Project description:All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group). BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%). On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group) and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models.

Dataset Information

Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers.

Publications

Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets