| 1. |
- Khorram-Manesh, Amir, 1958, et al.
(author)
-
The effect of opioids on the development of postoperative intra-abdominal adhesions.
- 2006
-
In: Digestive diseases and sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 51:3, s. 560-5
-
Journal article (peer-reviewed)abstract
- People addicted to opium rarely develop intra-abdominal adhesions after abdominal surgery. We aimed to evaluate the effect of opium or morphine on preventing postoperative adhesions in rats. Sixty-three rats were randomly divided into a control group, opium-addicted group, and morphine-addicted group in a double-blind study. Drug dependency was checked by using naloxone. Animals were then operated on and the cecum was abraded. At reoperation 3 weeks later the magnitude of adhesions was evaluated by a scoring system. There was a significant difference between the control, opium-addicted, and morphine-addicted groups with regard to the length (P < .001), thickness (P < .05), and severity of adhesions (P < .05). Opium or morphine reduces the severity of postoperative adhesions. Elucidation of the opioid receptor(s) involved in this process would enable the use of selective ligands and offer a pharmacologic strategy in preventing adhesion formation.
|
|
| 2. |
- Novotny, Ann, 1982, et al.
(author)
-
A pharmacological analysis of the cholinergic regulation of urokinase-type plasminogen activator secretion in the human colon cancer cell line, HT-29.
- 2010
-
In: European journal of pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 646:1-3, s. 22-30
-
Journal article (peer-reviewed)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.
|
|
| 3. |
|
|
| 4. |
- Nylund, Gunnar, 1959
(author)
-
Cell signalling in cancer. A functional and immunochemical investigation of purinergic,adrenergic, nitrergic, and prostaglandin mediated signalling mechanisms in experimental and human cancer
- 2004
-
Doctoral thesis (other academic/artistic)abstract
- Disturbed cell signalling is a hallmark of the cancer cell, being one important mechanismbehind uncontrolled cell growth. In the current study, we have investigated cancer cellsignalling with the focus on some first messenger and/or their receptors, in the murine celllines, MCG 101, and K1735-M2, and the human colon cancer cell line, HT-29. The signallingmolecules investigated were noradrenaline, prostaglandin E2 (PGE2), adenosine-5 L-triphosphate (ATP), and nitric oxide (NO).Functional investigations were undertaken by microphysiometry, which method allows forthe monitoring in real time of extracellular acidification rate (ECAR). This is a measure of theongoing metabolic activity of the cell, and how the challenging of the cell with a ligand mayaffect this variable. In addition, we investigated protein expression by immunochemicalmethods.Noradrenaline caused increased ECAR in the three cell lines. In the MCG 101 and K1735-M2, the membrane receptor involved was found to be the À3-adrenoceptor.PGE2 affected ECAR only in the MCG 101. Moreover, in this cell line, we foundindications of an autocrine loop, in which PGE2 may upregulate cyclooxygenase, the enzymeresponsible for prostanoid synthesis.ATP increased ECAR in the MCG 101, most likely via the P2Y2-purinoceptor subclass.In the HT-29, this ligand caused a biphasic effect on ECAR (increase followed by decrease).Both effects appeared to be elicited via the same receptor; this could be P2Y2, but aninvolvement of also P2Y4 cannot be excluded.In human colon cancer, the P2Y2-, and P2Y4-purinoceptors were significantly overexpressed,compared to adjacent, macroscopically tumour-free colon tissue.The inducible isoform of NO synthase (iNOS) was identified in the MCG 101. The findingthat also nitrotyrosine was expressed in these cells could suggest that iNOS was catalyticallyactive, resulting in the formation of peroxynitrite and, secondarily, nitrotyrosine. The tumourcells were, however, unaffected functionally by the administration of a eNO-donor f (sodiumnitroprusside), which may indicate that NO does not serve a function as e.g. anautocrine/paracrine growth factor for these cells.It is concluded that microphysiometry is a valuable tool for the investigation of functionalreceptors in tumour cells. Of the signalling molecules investigated in the current study, ATPappears to be of considerable interest for e.g. colon cancer.
|
|
| 5. |
- Nylund, Gunnar, 1959, et al.
(author)
-
Effects of norepinephrine or prostaglandin E2 on extracellular acidification rate of MCG 101, or K1735-M2 tumor cells
- 2004
-
In: Life Sci. - : Elsevier BV. - 0024-3205. ; 75:14, s. 1747-59
-
Journal article (peer-reviewed)abstract
- We studied by microphysiometry functional effects of two different signalling molecules in the murine tumor cell lines, MCG 101 and K1735-M2, namely norepinephrine (NE) and prostaglandin E2 (PGE2). This methodology implies estimation of intracellular metabolism by measurements of extracellular acidification rate (ECAR). MCG 101 (an undifferentiated, epithelial-like tumor), in contrast to K1735-M2 (a melanoma), has been found to produce great amounts of PGE2. Challenge of MCG 101 cells with PGE2 (0.284 and 2.84 microM for 9 min) elicited an increase in ECAR by about 10 and 41% above basal level, respectively. Pretreatment with indomethacin (0.5 microM) reduced the response to the two PGE2 concentrations by about 70 and 25%, respectively. In contrast, PGE2 caused virtually no response in K1735-M2 cells. Moreover, NE caused increases in ECAR in both cell types, possibly via beta3-adrenoceptors, as investigated pharmacologically in MCG 101, and by immunocytochemistry in both cell lines. The results obtained strongly suggest functional receptors for PGE2 in MCG 101, but not K1735-M2 tumor cells. Functional receptors for NE were demonstrated in both cell lines. There is possibly an autocrine loop in the MCG 101 cells, in which PGE2 activates cyclooxygenase.
|
|
| 6. |
- Nylund, Gunnar, 1959, et al.
(author)
-
Expression of P2Y2 purinoceptors in MCG 101 murine sarcoma cells, and HT-29 human colon carcinoma cells
- 2004
-
In: Autonomic neuroscience. - : Elsevier BV. - 1566-0702. ; 112:1-2, s. 69-79
-
Journal article (peer-reviewed)abstract
- We investigated how agonists at purinoceptors may affect tumour cell metabolism. This was investigated in vitro in tumour cell lines by microphysiometry, which method monitors extracellular acidification rate (ECAR), on-line. The cell lines investigated were the murine sarcoma, MCG 101, and the human colon cancer, HT-29. In MCG 101, adenosine-5'-triphosphate (ATP) or uridine-5'-triphosphate (UTP) caused a concentration-dependent increase in ECAR, most likely due to the ligation of P2Y(2) receptors, which response was blocked by suramin. In HT-29, ATP or UTP elicited a concentration-dependent, biphasic change in ECAR (increase/decrease). The pharmacological analysis suggests the involvement of P2Y(2) receptors, although other P2 receptor subtypes cannot be entirely excluded. This biphasic response to UTP or ATP was resistant to suramin. The expression of P2Y(2) receptors was demonstrated in both cell lines by immunocytochemistry and Western blot. The current study, thus, shows the functional and morphological expression of a purinoceptor subtype with partly different effects on metabolism in two different tumour cell lines.
|
|
| 7. |
- Nylund, Gunnar, 1959, et al.
(author)
-
Functional expression of mu-opioid receptors in the human colon cancer cell line, HT-29, and their localization in human colon.
- 2008
-
In: Digestive diseases and sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 53:2, s. 461-6
-
Journal article (peer-reviewed)abstract
- We have investigated the functional expression of mu-opioid receptors (MORs) in the human colon cancer cell line, HT-29. As revealed by immunocytochemistry, immunoreactivity was present in both the cytoplasm and nuclei of the cells. Challenge with morphine for 24 h (1 nM to 1 microM) barely affected cell proliferation, while the secretion of urokinase type plasminogen activator (a protease involved in invasion/metastasis) was markedly augmented by a concentration of 0.1 microM. Human colon cancer tissue from 14 consecutively operated patients was investigated by immunohistochemistry. MORs were found in the nuclei of colonocytes and immune cells of the lamina propria in tumor-free tissue. In tumor tissue, immunoreactivity was found in the membrane and often in the nuclei of tumor cells. The current findings suggest that morphine administration could affect tumor progression by interfering with, for example, invasive properties. Our demonstration of a nuclear expression of the MORs appears to be a novel finding.
|
|
| 8. |
- Pettersson, Ann, 1982, et al.
(author)
-
Is acetylcholine an autocrine/paracrine growth factor via the nicotinic alpha7-receptor subtype in the human colon cancer cell line HT-29?
- 2009
-
In: European journal of pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 609:1-3, s. 27-33
-
Journal article (peer-reviewed)abstract
- We used immunochemistry to demonstrate expression of acetylcholine's nicotinic alpha7-receptor subtype in human colon cancer cell line HT-29. Moreover, RT-PCR and immunochemistry showed that choline acetyltransferase and acetylcholine esterase, the enzymes responsible for acetylcholine synthesis and degradation, respectively, localise in HT-29 cells. Bromoacetylcholine bromide, an inhibitor of choline acetyltransferase, significantly attenuated basal cell growth. Our findings suggest that acetylcholine might serve as an autocrine/paracrine-or speculatively, even intracrine-signalling molecule in cell line HT-29, thus contributing to carcinogenesis/cancer progression.
|
|
| 9. |
- Pettersson, Ann, 1982-, et al.
(author)
-
Nicotine induced modulation of SLURP-1 expression in human colon cancer cells.
- 2009
-
In: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1872-7484 .- 1566-0702. ; 148:1-2, s. 97-100
-
Journal article (peer-reviewed)abstract
- The secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is an endogenous ligand at the alpha 7 subunit of the nicotinic acetylcholine receptor (nAChR). SLURP-1 has anti-tumourigenic properties. In the current study, we demonstrate that the challenge of HT-29 human colon cancer cells with nicotine for 24 h to increase cell growth via the alpha 7nAChRs, caused a marked reduction of the protein expression of SLURP-1. We suggest that there is an interplay between acetylcholine and SLURP-1 in the HT-29 cells, both molecules serving as autocrine growth controlling ligands at the alpha 7nAChR, where acetylcholine regulates the release of SLURP-1.
|
|
