[Show abstract][Hide abstract] ABSTRACT: Stromal macrophages of different phenotypes can contribute to the expression of proteins that affects metastasis such as urokinase-type plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor-1 (PAI-1), but knowledge of how essential their contribution is in comparison to the cancer cells in small cell lung cancer (SCLC) and lung squamous cell carcinoma (SCC) is lacking. The expression of uPA, uPAR, and PAI-1 and of the matrix metalloproteinases (MMP)-2 and MMP-9 were studied in human macrophages of M1 and M2 phenotype and compared to a lung SCC (NCI-H520) and a SCLC (NCI-H69) cell line. Effects of treatment with conditioned media (CM) from M1 and M2 macrophages on the expression of these genes in H520 and H69 cells as well as effects on the cell growth were investigated. In addition, data on the stromal macrophages immunoreactivity of uPAR, MMP-2, and MMP-9 in a few SCC and SCLC biopsies was included. uPAR, MMP-2, and MMP-9 were confirmed in stromal cells including macrophages in the SCC and SCLC biopsies. In vitro, both macrophage phenotypes expressed considerably higher mRNA levels of uPA, uPAR, PAI-1, and MMP-9 compared to the cancer cell lines, and regarding uPAR, the highest level was found in the M1 macrophage phenotype. Furthermore, M1 CM treatment not only induced an upregulation of PAI-1 in both H520 and H69 cells but also inhibited cell growth in both cell lines, giving M1 macrophages both tumor-promoting and tumor-killing potential.
[Show abstract][Hide abstract] ABSTRACT: Resistance of tumor cells to chemotherapy, such as 5‑fluorouracil (5‑FU), is an obstacle for successful treatment of cancer. As a follow‑up of a previous study we have investigated the effect of conditioned media (CM) from macrophages of M1 or M2 phenotypes on 5‑FU cytotoxicity on the colon cancer cell lines HT‑29 and CACO‑2. HT‑29 cells, but not CACO‑2 cells, having been treated with a combination of M1 CM and 5‑FU recovered their cell growth to a much larger extent compared to cells having been treated with 5‑FU alone when further cultured for 7 days in fresh media. M1 CM treatment of HT‑29, but not CACO‑2 cells, induced cell cycle arrest in the G0/G1 and G2/M phases. 5‑FU treatment induced accumulation of cells in S‑phase in both HT‑29 and CACO‑2 cells. This accumulation of cells in S‑phase was attenuated by combined M1 CM and 5‑FU treatment in HT‑29 cells, but not in CACO‑2 cells. The mRNA expression of cell cycle regulatory proteins and 5‑FU metabolic enzymes were analyzed in an attempt to find possible mechanisms for the M1 CM induced attenuation of 5‑FU cytotoxicity in HT‑29. Thymidylate synthetase (TS) and thymidine phosphorylase (TP) were found to be substantially downregulated and upregulated, respectively, in HT‑29 cells treated with M1 CM, making them unlikely as mediators of reduced 5‑FU cytotoxicity. Among cell cycle regulating proteins, p21 was induced in HT‑29 cells, but not in CACO‑2 cells, in response to M1 CM treatment. However, small interfering RNA (siRNA) knockdown of p21 had no effect on the M1 CM induced cell cycle arrest seen in HT‑29 and neither did it change the growth recovery after combined treatment of HT‑29 cells with M1 CM and 5‑FU. In conclusion, treatment of HT‑29 cells with M1 CM reduces the cytotoxic effect of 5‑FU and this is mediated by a M1 CM induced cell cycle arrest in the G0/G1 and G2/M phases. So far, we lack an explanation why this action is absent in the CACO‑2 cells. The current findings may be important for optimization of chemotherapy in colon cancer.
International Journal of Oncology 10/2014; 46(1). DOI:10.3892/ijo.2014.2696 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nitric oxide (NO) production from the bladder wall in patients with Bladder Pain Syndrome (BPS) Type 3C is increased compared to undetectable NO levels in non-Hunner BPS patients and healthy controls. However, the underlying mechanism/s of the increased NO production is largely unknown. Our aim was to compare mRNA expression of a selected group of cytokines in BPS/IC Type 3C patients versus pain-free controls.
Cold cup biopsies from seven BPS Type 3C patients and six healthy subjects were analysed; mRNA expressions of IL-4, IL-6, IL-10, IL-17A, iNOS, TNF-α, TGF-β and IFN-γ were estimated by real time PCR. The protein expression of IL-17 was determined with immunohistochemistry. Mast cell tryptase labelling was used to evaluate the appearance and count of mast cells.
The mRNA levels of IL-6, IL-10, IL-17A and iNOS, as well as the numbers of mast cells infiltrating the bladder mucosa, were significantly increased in BPS Type 3C patients as compared with healthy subjects. TNF-α, TGF-β and IFN-γ mRNA were similar in patients and controls. The expression of IL-17A at the protein level was up-regulated and localised to inflammatory cells and urothelium in the BPS Type 3C patients.
BPS/IC patients had increased mRNA levels of IL-17A, IL-10, IL-6 and iNOS. IL-17A might be an important player in the inflammatory process. The increase in IL-17A is a novel finding that may have new treatment implications.
The Journal of urology 05/2014; 192(5). DOI:10.1016/j.juro.2014.04.099 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interstitial cystitis is regarded as a heterogenous syndrome with two distinguishable forms: the non-ulcer and the classic form of interstitial cystitis, the latter with Hunner's lesions; or bladder pain syndrome type 3C and non-Hunner bladder pain syndrome, respectively.
A cohort of 379 patients diagnosed with interstitial cystitis was studied. Nitric oxide release from the bladder was measured using a chemiluminescence nitric oxide analyzer. Bladder biopsies from the patients and healthy controls were analyzed by routine histopathological examination. Biopsies from a subset of patients and controls were also analyzed by immunohistochemistry and cytokine gene expression by real-time polymerase chain reaction.
Patients with bladder pain syndrome type 3C/classic interstitial cystitis had considerably higher levels of nitric oxide as compared with non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients and healthy individuals, and showed histologically a chronic inflammation in the bladder mucosa, with abundant mast cell infiltration in all layers of the bladder wall. No inflammation was noted in non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients. The isoenzymes inducible nitric oxide synthase, the catalyst in the nitric oxide production, was strongly expressed in the inflammatory cells in the bladder mucosa of bladder pain syndrome type 3C/classic interstitial cystitis patients. In addition, the expression of the pro-inflammatory cytokines interleukin-6 and interleukin-17A messenger ribonucleic acid, and of anti-inflammatory interleukin-10 messenger ribonucleic acid showed significantly increased levels in bladder pain syndrome type 3C/classic interstitial cystitis compared with healthy controls.
Bladder pain syndrome type 3C/classic interstitial cystitis is a distinct inflammatory disease and in many aspects shares features of inflammatory autoimmune diseases. These findings could open up novel research avenues with expectations for new targets for pharmacological treatment.
International Journal of Urology 04/2014; 21 Suppl S1:75-78. DOI:10.1111/iju.12370 · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Solid tumors are infiltrated by stroma cells including macrophages and these cells can affect tumor growth, metastasis and angiogenesis. We have investigated the effects of conditioned media (CM) from different macrophages on the proliferation of the colon cancer cell lines HT-29 and CACO-2. CM from THP-1 macrophages and monocyte‑derived human macrophages of the M1 phenotype, but not the M2 phenotype, inhibited proliferation of the tumor cells in a dose‑dependent manner. Lipopolysaccaharide and interferon γ was used for differentiation of macrophages towards the M1 phenotype and CM were generated both during differentiation (M1DIFF) and after differentiation (M1). M1 and M1DIFF CM as well as THP-1 macrophage CM resulted in cell cycle arrest in HT-29 cells with a decrease of cells in S phase and an increase in G2/M phase. Treatment of HT-29 cells with M1DIFF, but not M1 or THP-1 macrophage CM, resulted in apoptosis of about 20% of the tumor cells and this was accompanied by lack of recovery of cell growth after removal of CM and subsequent culture in fresh media. A protein array was used to identify cytokines released from M1 and M2 macrophages. Among the cytokines released by M1 macrophages, tumor necrosis factor α and CXCL9 were tested by direct addition to HT-29 cells, but neither affected proliferation. Our results indicate that M1 macrophages inhibit colon cancer cell growth and have the potential of contributing to reducing tumor growth in vivo.
International Journal of Oncology 12/2013; 44(2). DOI:10.3892/ijo.2013.2203 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Bladder pain syndrome/interstitial cystitis (BPS/IC) includes a heterogeneous collection of underlying pathological conditions. Compared to the classic IC with a Hunner lesion, now denominated ESSIC type 3C, the non-Hunner type of BPS/IC appears different in a number of respects. In a previous study, measuring luminal nitric oxide (NO) in the bladder of patients with BPS/IC, it was reported that all patients with ESSIC type 3C had high levels of NO. The aim of the present study was to investigate the source of inducible nitric oxide synthase (iNOS) and thereby the cellular origin of NO production via iNOS.
Material and methods:
Immunohistochemistry, with two different anti-iNOS antibodies, was used to study 10 patients with BPS/IC ESSIC type 3C who expressed high levels of intraluminal NO. These results were compared with four patients with non-Hunner BPS/IC. To substantiate further the involvement of iNOS in this condition, the protein expression of nitrotyrosine, a marker for iNOS activation, was also assessed.
On routine histopathology, the tissues of type 3C patients exhibited inflammatory infiltrates of varying intensity. Strong immunoreactivity for both iNOS and nitrotyrosine was noted within the urothelium but also within the inflammatory infiltrates in the lamina propria of these subjects.
The findings of a clearly detectable protein expression of iNOS in both the urothelium and the inflammatory infiltrates in bladder biopsies from patients with BPS/IC ESSIC type 3C suggest that the production of NO, in this entity, may occur in different tissue compartments.
Scandinavian Journal of Urology and Nephrology 07/2012; 47(1). DOI:10.3109/00365599.2012.699100 · 1.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ischemic preconditioning (IPC) of an organ may induce protection against the injury caused by longer duration of ischemia and subsequent reperfusion. In a standardized model of such injury in the rat liver, we used the following protocol to investigate whether adenosine played a role in IPC by preventing its enzymatic degradation by dipyridamole pretreatment according to the following protocol: group 1, nonischemic control rats; group 2, ischemic control rats subjected to 60 minutes of ischemia by clamping of the common hepatic artery followed by 60 minutes of reperfusion; group 3, IPC with 10 minutes of ischemia followed by 15 minutes of reperfusion, prior to the ischemia/reperfusion period as in group 2; group 4, pharmacologic preconditioning with administration of dipyridamole prior to the ischemia/reperfusion period as in group 2. Peripheral liver blood flow was significantly reduced during clamping (groups 2 to 4). After unclamping, blood flow was still reduced in the ischemic rats (group 2) but had returned to preclamp values in the animals that had been subjected to ischemic (group 3) or pharmacologic (group 4) preconditioning. Liver cell injury was significantly increased in the ischemia group (group 2) only. In our experimental model of ischemia/reperfusion injury in the rat liver, we found an equally beneficial effect with ischemic and pharmacologic preconditioning. Adenosine appears to be a crucial factor in IPC.
Journal of Gastrointestinal Surgery 04/2012; 4(1):44-9. DOI:10.1016/S1091-255X(00)80031-1 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various markers of the cholinergic system (like e.g. choline acetyltransferase) were demonstrated by immunohistochemistry in, seemingly, β-cells of rat pancreas. The findings may suggest an autocrine role of acetylcholine for the β-cells.
[Show abstract][Hide abstract] ABSTRACT: Signaling molecules in the gastrointestinal (GI) tract, as released from intrinsic, or extrinsic neurons, or from local endocrine cells may serve as positive or negative growth factors, and it has been suggested that such could participate also in colorectal carcinogenesis/cancer progression. Sporadic colorectal cancer arises from an initially benign adenoma, which, in turn, develops from the stem cell compartment, located in the bottom of the crypts of the colorectal mucosa. It was recently demonstrated in rat that intrinsic denervation of the colon appeared to be protective against chemically induced carcinogenesis. Of the various GI signaling molecules, noradrenaline (NA) and substance P (SP) may be of particular importance as growth factors involved in colorectal cancer. In the current issue of Neurogastroenterology and Motility, Graf et al. demonstrate that in benign, human colon polyps, there was a loss of innervation compared with adjacent mucosa, affecting efferent, noradrenergic, as well as sensory, SP‐ergic fibers, while there was an increase in SP‐immunoreactive non‐neuronal cells in the polyps. The results obtained could suggest that loss of mucosal innervation, due to e.g. luminal, pro‐inflammatory stimuli, could result in unbalanced pro‐tumorigenic stimulation of the stem cell region by non‐neuronal SP. The current findings may be important for the further understanding of the development of sporadic colorectal cancer.
Neurogastroenterology and Motility 02/2012; 24(2). DOI:10.1111/j.1365-2982.2011.01854.x · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The triggers of the acute local inflammatory response to peritoneal dialysis (PD) fluid exposure remain unknown. In the present study, we investigated the effects of neurogenic inflammation and mast cell degranulation on water and solute transport in experimental PD.
Single 2-hour dwells in rats with PD catheters were studied. Histamine and the neuropeptides substance P and calcitonin gene-related peptide (CGRP) were measured in PD fluid samples by ELISA. Radiolabeled albumin ((125)I and (131)I respectively) was used as an intraperitoneal (IP) and intravascular tracer. Glucose and urea concentrations were measured in plasma and PD fluid. The effects of varying the volume and osmolarity of a lactate-buffered PD fluid were compared and related to the effects of pharmacologic intervention.
Application of 20 mL 3.9% glucose PD fluid induced an IP histamine release during the first 30 minutes, blockable by the mast cell stabilizer doxantrazole and the substance P neurokinin-1 receptor (NK1R)-blocker spantide. Histamine release was also inhibited at a reduced PD volume (14 mL), but was not affected by normalizing the PD fluid osmolarity. Blockade of NK1R also reduced plasma albumin leakage to the peritoneal cavity. Inhibition of CGRP receptors by CGRP8-37 improved osmotic (transcapillary) and net ultrafiltration and reduced the dialysate urea concentration. Neuropeptide release was not clearly related to activation of the TrpV1 receptor, the classic trigger of neurogenic inflammation.
Neuropeptide release exaggerated albumin loss and reduced ultrafiltration in this rat PD model. Intervention aimed at the neuropeptide action substantially improved PD efficiency.
[Show abstract][Hide abstract] ABSTRACT: 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 α7-subtype of the nicotinic ACh receptors, and the peptide ligand at the α7 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: The integration of living, human smooth muscle cells in biosynthesized cellulose scaffolds was monitored by nonlinear microscopy toward contractile artificial blood vessels. Combined coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy was applied for studies of the cell interaction with the biopolymer network. CARS microscopy probing CH(2)-groups at 2845 cm(-1) permitted three-dimensional imaging of the cells with high contrast for lipid-rich intracellular structures. SHG microscopy visualized the fibers of the cellulose scaffold, together with a small signal obtained from the cytoplasmic myosin of the muscle cells. From the overlay images we conclude a close interaction between cells and cellulose fibers. We followed the cell migration into the three-dimensional structure, illustrating that while the cells submerge into the scaffold they extrude filopodia on top of the surface. A comparison between compact and porous scaffolds reveals a migration depth of <10 μm for the former, whereas the porous type shows cells further submerged into the cellulose. Thus, the scaffold architecture determines the degree of cell integration. We conclude that the unique ability of nonlinear microscopy to visualize the three-dimensional composition of living, soft matter makes it an ideal instrument within tissue engineering.
[Show abstract][Hide abstract] 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 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 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.
European journal of pharmacology 11/2010; 646(1-3):22-30. DOI:10.1016/j.ejphar.2010.08.004 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Secretion from the lacrimal gland is an important part of the well-being of the eye, and a central part in the search for treatment of dry eye syndrome. Adenosine has stimulatory effects on the lacrimal gland, and can potentiate the effect of the cholinergic agonist carbachol (Cch). The aim of the present study is to investigate the presence of the adenosine A(2) receptor subtypes A(2A) and A(2B) in the rabbit lacrimal gland, and to characterize their role in regulated acinar cell secretion.
Expression of the receptors was investigated using reverse transcriptase-PCR (RT-PCR) and immunofluorescence, and secretion effects were studied using a secretion assay in isolated lacrimal gland acinar cells.
Presence of both receptors was detected by RT-PCR and immunofluorescence. The secretion assay revealed a minor effect of stimulation of the A(2) receptors, and a strong synergistic effect with the cholinergic agonist Cch. The synergistic effect was significantly reduced by the A(2B) antagonist PSB 1115, but not by the A(2A) antagonist SCH 58261, indicating that A(2B) is the receptor responsible for this potentiation.
The study reveals the presence of the adenosine A(2) receptor subtypes as well as a role for them in lacrimal gland secretion, and especially in the synergy with purinergic and cholinergic stimulation.
Current eye research 06/2010; 35(6):466-74. DOI:10.3109/02713681003602667 · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)), a tetrapeptide present in the enzymatic digest of bovine beta-casein, is a selective ligand of the mu-opioid receptor. In the present study, we describe the synthesis of a series of novel morphiceptin analogs modified in positions 1-3. Two of the obtained analogs, [Dmt(1), D-Ala(2), D-1-Nal(3)]morphiceptin and [Dmt(1), D-NMeAla(2), D-1-Nal(3)]morphiceptin (Dmt-2',6'-dimethyltyrosine and d-1-Nal-3-(1-naphthyl)-D-alanine)) displayed very high mu-receptor affinity, resistance to enzymatic degradation, and remarkable supraspinally mediated analgesia, as shown in the hot-plate test after intracerebroventricular but not intravenous administration, which indicated that they could not cross the blood-brain barrier. Therefore, these two analogs were further tested in vitro and in vivo towards their possible peripheral analgesic activity and inhibitory effect on gastrointestinal (GI) motility. We report that both peptides showed strong antinociceptive effect in the writhing test after intraperitoneal administration, inhibited smooth muscle contractility in vitro and GI motility in vivo. Taken together, these findings indicate that the novel morphiceptin analogs which induce peripheral, but not central antinociception, inhibit GI transit, and possess exceptional metabolic stability, may provide an interesting approach to the development of peripherally restricted agents for the treatment of GI motility disorders, such as diarrhea or diarrhea-predominant irritable bowel syndrome.
[Show abstract][Hide abstract] ABSTRACT: 1 Possibly acting via mu-opioid receptors (MORs), morphine inhibits the formation of experimentally induced postoperative abdominal adhesions in rats. Mesothelial cells may participate in adhesion formation by secreting mediators that interfere negatively with fibrinolysis. Morphine may prevent adhesions by inhibiting the release of pro-adhesion mediators from mesothelial cells. This study aimed to investigate whether human mesothelial cells express MOR-1; if so, such could constitute a site of action for morphine in adhesion prevention. 2 Cells from Met-5A, a human mesothelial cell line were seeded and prepared for immunocytochemistry and Western blotting. 3 Immunocytochemistry showed MOR-1 expression in mesothelial cells, predominantly in the nuclei. Western blotting showed two bands (c. 35 and 50 kDa) which correspond to those obtained with a control lysate from cells known to express MORs. In addition, we found MOR-1 expression with nuclear and cytoplasmatic localization in biopsies from human abdominal adhesions. 4 The current findings may suggest that morphine could interact directly with mesothelial cells via MOR-1 receptors, and thereby modulate adhesion formation, possibly by interfering with the release of pro-adhesion factors from these cells.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the cellular and molecular expression of tartrate resistant acid phosphatase (TRAP) as a marker of activated macrophages in macrophage dependent dextran sulphate sodium (DSS)-induced colitis in rats. In normal colon, TRAP+/CX(3)CR(1)+ macrophages were located in the upper part of the lamina propria. In the early stage (day 1-3) of acute colitis prior to histopathological changes, induction of the cytokines TNFalpha, IL-12 and IFN gamma occurred concomitant with increased mRNA and enzyme activity of TRAP along with a slight increase of TRAP immunolabelling in macrophages of the upper lamina propria, suggesting induction of TRAP in resident macrophages. Among these cytokines, TNFalpha up-regulated TRAP expression in the RAW 264.7 monocyte/macrophage cell line. In a later phase (day 7) with fulminant colitis, a massive infiltration of macrophages including recruited TRAP+/CCR2+ cells was observed also in the lower part of the lamina propria as well as in the submuscular layer. Additionally, differentiated cellular expression of pro- and mature TRAP also suggest that mucosal macrophages in the lower part of lamina propria bordering the sub-mucosa provide a source of replenishment of macrophages situated in the upper lamina propria. In conclusion, induction of TRAP provides an early sign of macrophage responsiveness in DSS induced colitis.
[Show abstract][Hide abstract] ABSTRACT: Urokinase plasminogen activator plays a key role in tumor-associated processes, increasing cancer cell invasion and metastasis, and is therefore used as a marker in cancer prognosis. In this study, we have determined the effect of mu-opioid receptor agonists and antagonists on the urokinase plasminogen activator secretion in MCF-7 cell line. It was shown that mu-opioid receptor agonists, such as morphine and endomorphins, greatly stimulate urokinase plasminogen activator secretion, while naloxone and MOR-selective antagonists elicit the opposite effect. The same tendency was observed also on the urokinase plasminogen activator mRNA level. However, neither agonists nor antagonists had any effect on proliferation of MCF-7 cells. The findings reported in this study may be useful in designing further experiments aimed at elucidating the role of the opioid system in cancer cells.
Chemical Biology & Drug Design 09/2009; 74(4):390-6. DOI:10.1111/j.1747-0285.2009.00875.x · 2.49 Impact Factor