| 1. |
- Delbro, Dick, et al.
(författare)
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Nuclear expression of mu-opioid receptors in a human mesothelial cell line
- 2009
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Ingår i: Autonomic & Autacoid Pharmacology. - : Wiley. - 1474-8665 .- 1474-8673. ; 29:4, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- 1 Possibly acting via mu-opioid receptors (MORs), morphine inhibits the formation ofexperimentally induced postoperative abdominal adhesions in rats. Mesothelial cells mayparticipate in adhesion formation by secreting mediators that interfere negatively withfibrinolysis. Morphine may prevent adhesions by inhibiting the release of pro-adhesionmediators from mesothelial cells. This study aimed to investigate whether human mesothelialcells express MOR-1; if so, such could constitute a site of action for morphine in adhesionprevention.2 Cells from Met-5A, a human mesothelial cell line were seeded and prepared forimmunocytochemistry and Western blotting.3 Immunocytochemistry showed MOR-1 expression in mesothelial cells, predominantly in thenuclei. Western blotting showed two bands (c. 35 and 50 kDa) which correspond to thoseobtained with a control lysate from cells known to express MORs. In addition, we foundMOR-1 expression with nuclear and cytoplasmatic localization in biopsies from humanabdominal adhesions.4 The current findings may suggest that morphine could interact directly with mesothelial cellsvia MOR-1 receptors, and thereby modulate adhesion formation, possibly by interfering withthe release of pro-adhesion factors from these cells
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| 2. |
- Novotny, Ann, 1982-, et al.
(författare)
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A pharmacological analysis of the cholinergic regulation of urokinase-type plasminogen activator, and plasminogen activator inhibitor-1 secretion in the human colon cancer cell line, HT-29
- 2010
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 646:1-3, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- Urokinase-type plasminogen activator (uPA) is an important factor for tumour cell invasion and metastasis. We recently showed that acetylcholine is an autocrine/paracrine growth factor for the human colon cancer cell line, HT-29, in part via the α7 subtype of the nicotinic acetylcholine receptors. In the current study, we investigated whether acetylcholine participates in the regulation of the protein expressions of also uPA and its receptor (uPAR) in the HT-29 cell line. Such were investigated by immunocytochemistry and Western blotting, and quantitation of uPA secretion was undertaken by ELISA. Stimulation of the cells for 24 h with nicotine caused increased uPA secretion with peak effect (78% above the control) occurring at a nicotine concentration of 10 nM. This effect was markedly inhibited by α-Bungarotoxin, thus showing the involvement of α7 nicotinic acetylcholine receptors. Basal uPA secretion was found to be partly dependent on ongoing activation of nicotinic receptors, suggesting tonic production of acetylcholine. Conversely, there was no cholinergic influence on the expression of uPAR. The current findings demonstrate novel aspects of receptor-mediated regulation of tumour metastatic potential via uPA secretion. This may suggest future pharmaceutical strategies in treatment of colorectal cancer.
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| 3. |
- Novotny, Ann, 1982, et al.
(författare)
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A pharmacological analysis of the cholinergic regulation of urokinase-type plasminogen activator secretion in the human colon cancer cell line, HT-29.
- 2010
-
Ingår i: European journal of pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 646:1-3, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- Urokinase-type plasminogen activator (uPA) is an important factor for tumour cell invasion and metastasis. We recently showed that acetylcholine is an autocrine/paracrine growth factor for the human colon cancer cell line, HT-29, in part via the alpha7 subtype of the nicotinic acetylcholine receptors. In the current study, we investigated whether acetylcholine participates in the regulation of the protein expressions of also uPA and its receptor (uPAR) in the HT-29 cell line. Such were investigated by immunocytochemistry and Western blotting, and quantitation of uPA secretion was undertaken by ELISA. Stimulation of the cells for 24h with nicotine caused increased uPA secretion with peak effect (78% above the control) occurring at a nicotine concentration of 10nM. This effect was markedly inhibited by alpha-Bungarotoxin, thus showing the involvement of alpha7 nicotinic acetylcholine receptors. Basal uPA secretion was found to be partly dependent on ongoing activation of nicotinic receptors, suggesting tonic production of acetylcholine. Conversely, there was no cholinergic influence on the expression of uPAR. The current findings demonstrate novel aspects of receptor-mediated regulation of tumour metastatic potential via uPA secretion. This may suggest future pharmaceutical strategies in treatment of colorectal cancer.
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| 4. |
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| 5. |
- Novotny, Ann, 1982, et al.
(författare)
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Is acetylcholine a signaling molecule for human colon cancer progression?
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 46:4, s. 446-455
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Non-neuronal acetylcholine (ACh) has been suggested to be a mediator for the development of various types of cancer. We analyzed a possible role for this molecule in carcinogenesis and/or progression of human colon cancer, in patient biopsies harvested from the colon during surgery. We addressed whether ACh synthesis (by choline acetyltransferase) and/or degradation (by ACh esterase), as well as the expression of the alpha alpha 7-subtype of the nicotinic ACh receptors, and the peptide ligand at the alpha alpha 7 receptors, secreted mammalian Ly6/urokinase-type plasminogen activator receptor-related protein-1, respectively, are deranged in tumor tissue as compared with macroscopically tumor-free colon tissue. Methods. A total of 38 patients were grouped for analysis based on their respective Dukes stage (either Dukes A ++ B or C ++ D). A mucosal tissue sample was harvested from macroscopically tumor-free colon tissue (i.e. control tissue), as well as from the tumor, and protein lysates were prepared for quantitative Western blotting. Full-thickness specimens were taken for immunohistochemistry. Results. For all the above named markers, there was a significant difference between control and tumor tissue with regard to protein levels, and there was, in addition, a significant difference in protein levels between the Dukes A ++ B and C ++ D groups. Conclusion. The current findings may suggest a role for ACh in colon carcinogenesis/cancer progression; the data obtained could have prognostic and/or therapeutic significance for this disease.
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| 6. |
- Vilhav, Caroline, et al.
(författare)
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Fractional uptake of circulating tumor cells into liver-lung compartments during curative resection of periampullary cancer.
- 2018
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Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 16:5, s. 6331-6338
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Tidskriftsartikel (refereegranskat)abstract
- Circulating tumor cells (CTCs) are able to predict outcome in patients with breast, colon and prostate cancer and appear to be promising biomarkers of pancreatic carcinoma. The aim of the present study was to demonstrate a statistically significant portal-arterial difference of CTCs during curative resection of periampullary cancer. A commercially available instrument (IsofluxR) was used to quantify blood content of CTC in 10 patients with periampullary cancer according to preoperative diagnostics. Portal and arterial blood samples (~8 ml each) were simultaneously collected intra-operatively following surgical dissection prior to division of the pancreas for tumor removal. Quantitative CTC analyses were performed according to standardized protocols for immune-magnetic enrichment of CTC. Flow cytometry was applied for qualitative evaluations of various CTC markers in 7 patients. There was a statistically significant difference in the number of CTCs collected in the portal blood [58±14 cells per 100 ml; mean ± standard error (SE)] vs. arterial blood [24±7 cells per 100 ml (SE), P<0.025]. A fractional uptake of ≥40% across liver and lung compartments of assumed malignant CTC was estimated to correspond to the appearance of ~410 tumor cells per minute during pancreatic resections based on estimated hepatic blood flow, measured tumor cell mass and tumor cell proliferation activity. Complications in the collection of portal blood were not observed. A significant uptake across liver or lung compartments of potentially malignant tumor CTCs from periampullary carcinoma may represent a model to capture, define and characterize cell clones with metastatic potential in liver and lung tissues following surgical resection.
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