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Rich66 · 12-28-2009, 10:16 PM

Br J Anaesth. 2009 Nov;103(5):685-90. Epub 2009 Sep 22.
Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro.

Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ.

Source

Department of Anaesthesia and Intensive Care Medicine, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.

Erratum in

Br J Anaesth. 2010 Apr;104(4):516.

Abstract

BACKGROUND:

Metastatic recurrence is the main cause of breast cancer-related deaths. Tumour cell proliferation and migration are crucial steps in the metastatic process. Several perioperative factors, including general anaesthesia and opioid analgesia, adversely affect immune function, potentially increasing metastatic recurrence. Regional anaesthesia-analgesia has been consistently shown to attenuate the stress response to surgery, and also reduce opioid and general anaesthesia requirements, thereby attenuating this perioperative immunosuppression. We investigated the effect of serum from breast cancer surgery patients who received different anaesthetic techniques on breast cancer cell function in vitro.
METHODS:

Patients were randomized to receive propofol/paravertebral anaesthesia-analgesia (propofol/paravertebral, n=11) or sevoflurane general anaesthesia with opioid analgesia (sevoflurane/opioid, n=11). The ER-negative MDA-MB-231 cell line was treated with patient serum from both groups. The effects on proliferation and migration were measured.
RESULTS:

Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathology. Pain scores were lower at 1 and 2 h in the propofol/paravertebral analgesia group. Compared with preoperative values, proliferation of MDA-MB-231 cells treated with postoperative patient serum at 10% concentration from the propofol/paravertebral group was significantly reduced compared with the sevoflurane/opioid group (-24% vs 73%, P=0.01). There was no significant change in MDA-MB-231 cell migration after treatment with patient serum between the two groups.

CONCLUSIONS:

Serum from patients receiving propofol/paravertebral anaesthesia for breast cancer surgery inhibited proliferation, but not migration, of ER-MDA-MB-231 cells in vitro, to a greater extent than that from patients receiving sevoflurane/opioid anaesthesia-analgesia. This implies that anaesthetic technique alters the serum molecular milieu in ways that may affect breast cancer cell function, possibly by altering anaesthetic and opioid drug administration and resultant pain scores.

PMID:: 19776028; [PubMed - indexed for MEDLINE]

Free full text

Br J Anaesth. 2010 Aug;105(2):106-15.
Effect of anaesthetic technique and other perioperative factors on cancer recurrence.

Snyder GL, Greenberg S.

Source

Department of Anesthesia and Perioperative Medicine, University of California San Francisco, 505 Parnassus Ave., San Francisco, CA 94143, USA. gabrielsnyder@hotmail.com

Abstract

Surgical excision is the mainstay of treatment for potentially curable solid tumours. Metastatic disease is the most important cause of cancer-related death in these patients. The likelihood of tumour metastases depends on the balance between the metastatic potential of the tumour and the anti-metastatic host defences, of which cell-mediated immunity, and natural killer cell function in particular, is a critical component. It is increasingly recognized that anaesthetic technique and other perioperative factors have the potential to effect long-term outcome after cancer surgery. Surgery can inhibit important host defences and promote the development of metastases. Anaesthetic technique and drug choice can interact with the cellular immune system and effect long-term outcome. The potential effect of i.v. anaesthetics, volatile agents, local anaesthetic drugs, opiates, and non-steroidal anti-inflammatory drugs are reviewed here. There is particular interest at present in the effect of regional anaesthesia, which appears to be beneficial. Retrospective analyses have shown an outcome benefit for paravertebral analgesia for breast cancer surgery and epidural analgesia for prostatectomy. Blood transfusion, pain, stress, and hypothermia are other potentially important perioperative factors to consider.

PMID:: 20627881; [PubMed - indexed for MEDLINE]

Anesth Analg. 2011 Oct 14. [Epub ahead of print]
Morphine-Induced Epidermal Growth Factor Pathway Activation in Non-Small Cell Lung Cancer.

Fujioka N, Nguyen J, Chen C, Li Y, Pasrija T, Niehans G, Johnson KN, Gupta V, Kratzke RA, Gupta K.
Source

From the *Department of Medicine, Division of Hematology, Oncology, Transplantation, University of Minnesota, Minneapolis;

Abstract

Background: Epidermal growth factor receptor (EGFR) is coactivated by the μ-opioid receptor (MOR), expressed on non-small cell lung cancer (NSCLC) cells and human lung cancer. We hypothesized that clinically used opioid analgesics that are MOR agonists coactivate EGFR, resulting in growth- and survival-promoting signaling.

Methods:We used H2009, a human adenocarcinoma NSCLC cell line, with constitutive EGFR phosphorylation, which showed increased expression of MOR and the δ-opioid receptor by reverse transcriptase polymerase chain reaction. We used Western immunoblotting, magnetic bead-based Bio-Plex cytokine assay, immunofluorescent staining, BrdU incorporation enzyme-linked immunosorbent assay, and BioCoat™ Matrigel™ invasion assay to examine cell signaling, cytokine expression, colocalization of MOR and EGFR in human lung cancer, and cell proliferation and invasion, respectively.

Results: Similar to epidermal growth factor (EGF), morphine stimulated phosphorylation of EGFR, Akt/protein kinase B (Akt), and mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) signaling in H2009 cells. Opioid receptor (OR) antagonist, naloxone, EGFR tyrosine kinase inhibitor, erlotinib, and silencing of MOR and δ-opioid receptor abrogated morphine- and EGF-induced phosphorylation of signaling, suggestive of OR-mediated coactivation of EGFR. H2009 cells secreted significantly higher levels of cytokines compared with control Beas2B epithelial cells. H2009-conditioned medium stimulated MOR expression in Beas2B cells, suggesting that cytokines secreted by H2009 may be associated with increased OR expression in H2009. We observed colocalization of EGFR and MOR, in human NSCLC tissue. Functionally, morphine- and EGF-induced proliferation and invasion of H2009 cells was ameliorated by naloxone as well as erlotinib.

Conclusion: Morphine-induced phosphorylation of EGFR occurs via ORs, leading to downstream MAPK/ERK, Akt phosphorylation, cell proliferation, and increased invasion. Notably, ORs are also associated with EGF-induced phosphorylation of EGFR. Increased coexpression of MOR and EGFR in human lung cancer suggests that morphine may have a growth-promoting effect in lung cancer.

PMID:: 22003224; [PubMed - as supplied by publisher]

12-28-2009, 10:16 PM	#6
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Opiates/Opioids Br J Anaesth. 2009 Nov;103(5):685-90. Epub 2009 Sep 22. Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro. Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ. Source Department of Anaesthesia and Intensive Care Medicine, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. Erratum in Br J Anaesth. 2010 Apr;104(4):516. Abstract BACKGROUND: Metastatic recurrence is the main cause of breast cancer-related deaths. Tumour cell proliferation and migration are crucial steps in the metastatic process. Several perioperative factors, including general anaesthesia and opioid analgesia, adversely affect immune function, potentially increasing metastatic recurrence. Regional anaesthesia-analgesia has been consistently shown to attenuate the stress response to surgery, and also reduce opioid and general anaesthesia requirements, thereby attenuating this perioperative immunosuppression. We investigated the effect of serum from breast cancer surgery patients who received different anaesthetic techniques on breast cancer cell function in vitro. METHODS: Patients were randomized to receive propofol/paravertebral anaesthesia-analgesia (propofol/paravertebral, n=11) or sevoflurane general anaesthesia with opioid analgesia (sevoflurane/opioid, n=11). The ER-negative MDA-MB-231 cell line was treated with patient serum from both groups. The effects on proliferation and migration were measured. RESULTS: Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathology. Pain scores were lower at 1 and 2 h in the propofol/paravertebral analgesia group. Compared with preoperative values, proliferation of MDA-MB-231 cells treated with postoperative patient serum at 10% concentration from the propofol/paravertebral group was significantly reduced compared with the sevoflurane/opioid group (-24% vs 73%, P=0.01). There was no significant change in MDA-MB-231 cell migration after treatment with patient serum between the two groups. CONCLUSIONS: Serum from patients receiving propofol/paravertebral anaesthesia for breast cancer surgery inhibited proliferation, but not migration, of ER-MDA-MB-231 cells in vitro, to a greater extent than that from patients receiving sevoflurane/opioid anaesthesia-analgesia. This implies that anaesthetic technique alters the serum molecular milieu in ways that may affect breast cancer cell function, possibly by altering anaesthetic and opioid drug administration and resultant pain scores. PMID: 19776028 [PubMed - indexed for MEDLINE] Free full text Br J Anaesth. 2010 Aug;105(2):106-15. Effect of anaesthetic technique and other perioperative factors on cancer recurrence. Snyder GL, Greenberg S. Source Department of Anesthesia and Perioperative Medicine, University of California San Francisco, 505 Parnassus Ave., San Francisco, CA 94143, USA. gabrielsnyder@hotmail.com Abstract Surgical excision is the mainstay of treatment for potentially curable solid tumours. Metastatic disease is the most important cause of cancer-related death in these patients. The likelihood of tumour metastases depends on the balance between the metastatic potential of the tumour and the anti-metastatic host defences, of which cell-mediated immunity, and natural killer cell function in particular, is a critical component. It is increasingly recognized that anaesthetic technique and other perioperative factors have the potential to effect long-term outcome after cancer surgery. Surgery can inhibit important host defences and promote the development of metastases. Anaesthetic technique and drug choice can interact with the cellular immune system and effect long-term outcome. The potential effect of i.v. anaesthetics, volatile agents, local anaesthetic drugs, opiates, and non-steroidal anti-inflammatory drugs are reviewed here. There is particular interest at present in the effect of regional anaesthesia, which appears to be beneficial. Retrospective analyses have shown an outcome benefit for paravertebral analgesia for breast cancer surgery and epidural analgesia for prostatectomy. Blood transfusion, pain, stress, and hypothermia are other potentially important perioperative factors to consider. PMID: 20627881 [PubMed - indexed for MEDLINE] Anesth Analg. 2011 Oct 14. [Epub ahead of print] Morphine-Induced Epidermal Growth Factor Pathway Activation in Non-Small Cell Lung Cancer. Fujioka N, Nguyen J, Chen C, Li Y, Pasrija T, Niehans G, Johnson KN, Gupta V, Kratzke RA, Gupta K. Source From the Department of Medicine, Division of Hematology, Oncology, Transplantation, University of Minnesota, Minneapolis; Abstract* Background: Epidermal growth factor receptor (EGFR) is coactivated by the μ-opioid receptor (MOR), expressed on non-small cell lung cancer (NSCLC) cells and human lung cancer. We hypothesized that clinically used opioid analgesics that are MOR agonists coactivate EGFR, resulting in growth- and survival-promoting signaling. Methods:We used H2009, a human adenocarcinoma NSCLC cell line, with constitutive EGFR phosphorylation, which showed increased expression of MOR and the δ-opioid receptor by reverse transcriptase polymerase chain reaction. We used Western immunoblotting, magnetic bead-based Bio-Plex cytokine assay, immunofluorescent staining, BrdU incorporation enzyme-linked immunosorbent assay, and BioCoat™ Matrigel™ invasion assay to examine cell signaling, cytokine expression, colocalization of MOR and EGFR in human lung cancer, and cell proliferation and invasion, respectively. Results: Similar to epidermal growth factor (EGF), morphine stimulated phosphorylation of EGFR, Akt/protein kinase B (Akt), and mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) signaling in H2009 cells. Opioid receptor (OR) antagonist, naloxone, EGFR tyrosine kinase inhibitor, erlotinib, and silencing of MOR and δ-opioid receptor abrogated morphine- and EGF-induced phosphorylation of signaling, suggestive of OR-mediated coactivation of EGFR. H2009 cells secreted significantly higher levels of cytokines compared with control Beas2B epithelial cells. H2009-conditioned medium stimulated MOR expression in Beas2B cells, suggesting that cytokines secreted by H2009 may be associated with increased OR expression in H2009. We observed colocalization of EGFR and MOR, in human NSCLC tissue. Functionally, morphine- and EGF-induced proliferation and invasion of H2009 cells was ameliorated by naloxone as well as erlotinib. Conclusion: Morphine-induced phosphorylation of EGFR occurs via ORs, leading to downstream MAPK/ERK, Akt phosphorylation, cell proliferation, and increased invasion. Notably, ORs are also associated with EGF-induced phosphorylation of EGFR. Increased coexpression of MOR and EGFR in human lung cancer suggests that morphine may have a growth-promoting effect in lung cancer. PMID: 22003224 [PubMed - as supplied by publisher]