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Hedlund, Petter
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Publications (10 of 114) Show all publications
Weinhold, P., Hennenberg, M., Strittmatter, F., Stief, C. G., Gratzke, C. & Hedlund, P. (2018). Transient receptor potential a1 (TRPA1) agonists inhibit contractions of the isolated human ureter.. Neurourology and Urodynamics, 37(2), 600-608
Open this publication in new window or tab >>Transient receptor potential a1 (TRPA1) agonists inhibit contractions of the isolated human ureter.
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2018 (English)In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 37, no 2, p. 600-608Article in journal (Refereed) Published
Abstract [en]

AIMS: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter.

METHODS: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence. The TRPA1 distribution was compared to TRPV1, calcitonin gene related peptide (CGRP), tyrosine hydroxylase (TH), and vimentin. Effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide (NaHS), and capsaicin (TRPV1 agonist) on human ureter preparations were studied in organ baths.

RESULTS: By Western blot, bands were detected at the expected molecular weight for TRPA1. TRPA1- and TRPV1-immunoreactivities were located on CGRP-positive nerves, but not on TH-positive nerves. TRPA1 was also located in vimentin-positive interstitial cells. In functional experiments, neither of the TRPA1-agonists (1-100 μM) had any direct effects on ureter tension (baseline/potassium-induced contractions). However, CA, AI, NaHS, and capsaicin (10 μM) decreased (P < 0.01-0.05) tetrodotoxin-sensitive electrically induced (2,4,8,16,32 Hz) contractions. Inhibitory activities were 50-61% (CA), 30-56% (AI), 30-40% (NaHS), and 37-67% (Capsaicin).

CONCLUSIONS: In the human ureter, TRPA1 is located to sensory nerves and interstitial cells. TRPA1 agonists inhibited electrically induced contractions but had no direct effect on smooth muscle tension of the human ureter. A role for TRPA1 in modulating neurotransmission and possibly peristalsis of the human ureter is proposed.

Keywords
H2S, TRPV1, ankyrin 1 nerve, cinnamaldehyde, contraction, interstitial cell, isothiocyanate
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-146136 (URN)10.1002/nau.23338 (DOI)28671709 (PubMedID)
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-04-13
Mistretta, F. A., Russo, A., Castiglione, F., Bettiga, A., Colciago, G., Montorsi, F., . . . Hedlund, P. (2016). DFL23448, A Novel Transient Receptor Potential Melastin 8-Selective Ion Channel Antagonist, Modifies Bladder Function and Reduces Bladder Overactivity in Awake Rats. Journal of Pharmacology and Experimental Therapeutics, 356(1), 200-211
Open this publication in new window or tab >>DFL23448, A Novel Transient Receptor Potential Melastin 8-Selective Ion Channel Antagonist, Modifies Bladder Function and Reduces Bladder Overactivity in Awake Rats
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2016 (English)In: Journal of Pharmacology and Experimental Therapeutics, ISSN 0022-3565, E-ISSN 1521-0103, Vol. 356, no 1, p. 200-211Article in journal (Refereed) Published
Abstract [en]

The transient receptor potential melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity is available. This study characterizes a new TRPM8-selective antagonist (DFL23448 [5-(2-ethyl-2H-tetrazol-5-yl)-2-(3-fluorophenyl)-1,3-thiazol-4-ol]) and evaluates it in cold-induced behavioral tests and tests on bladder function and experimental bladder overactivity in vivo in rats. DFL23448 displayed IC50 values of 10 and 21 nM in hTRPM8 human embryonic kidney 293 cells activated by Cooling Agent 10 or cold, but it had limited activity (IC50 &gt; 10 mu M) at transient receptor potential vanilloids TRPV1, TRPA1, or TRPV4 or at various G protein-coupled receptors. In rats, DFL23448 administered intravenously or orally had a half-life of 37 minutes or 4.9 hours, respectively. DLF23448 (10 mg/kg i.v.) reduced icilin-induced "wet dog-like" shakes in rats. Intravesical DFL23448 (10 mg/l), but not vehicle, increased micturition intervals, micturition volume, and bladder capacity. During bladder overactivity by intravesical prostaglandin E-2 (PGE(2)), vehicle controls exhibited reductions in micturition intervals, micturition volumes, and bladder capacity by 37%-39%, whereas the same parameters only decreased by 12%-15% (P &lt; 0.05-0.01 versus vehicle) in DFL23448-treated rats. In vehicle-treated rats, but not in DFL23448-treated rats, intravesical PGE(2) increased bladder pressures. Intravenous DFL23448 at 10 mg/kg, but not 1 mg/kg DFL23448 or vehicle, increased micturition intervals, micturition volumes, and bladder capacity. During bladder overactivity by intravesical PGE(2), micturition intervals, micturition volumes, and bladder capacity decreased in vehicle- and 1 mg/kg DFL23448-treated rats, but not in 10 mg/kg DFL23448-treated rats. Bladder pressures increased less in rats treated with DFL23448 10 mg/kg than in vehicle-or 1 mg/kg DFL23448-treated rats. DFL23448 (10 mg/kg i.v.), but not vehicle, prevented cold stress-induced bladder overactivity. Our results support a role for bladder TRPM8-mediated signals in experimental bladder overactivity.

Place, publisher, year, edition, pages
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124099 (URN)10.1124/jpet.115.228684 (DOI)000366942000021 ()26546575 (PubMedID)
Note

Funding Agencies|Dompe Pharmaceuticals; Gester Foundation

Available from: 2016-01-25 Created: 2016-01-19 Last updated: 2017-11-30
Fuellhase, C., Schreiber, A., Giese, A., Schmidt, M., Montorsi, F., Gratzke, C., . . . Hedlund, P. (2016). Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats. Neurourology and Urodynamics, 35(4), 464-470
Open this publication in new window or tab >>Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats
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2016 (English)In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 35, no 4, p. 464-470Article in journal (Refereed) Published
Abstract [en]

AimsTo test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors. MethodsMale rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5g rimonabant (CB1 antagonist) or 5g SR144528 (CB2 antagonist) were studied in awake rats. ResultsAfter administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH. ConclusionsUrodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. (c) 2015 Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
Keywords
AM251; bladder; endocannabinoid; obstruction; oleoyl ethyl amide; overactivity; rimonabant; SR144528
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128147 (URN)10.1002/nau.22753 (DOI)000374304900006 ()25788026 (PubMedID)
Note

Funding Agencies|German Research Foundation (DFG) [GR3333/2-1]; Gester Foundation, Sweden

Available from: 2016-05-19 Created: 2016-05-19 Last updated: 2017-11-30
Aizawa, N., Gandaglia, G., Hedlund, P., Fujimura, T., Fukuhara, H., Montorsi, F., . . . Igawa, Y. (2016). URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E-2-induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats. BJU International, 117(5), 821-828
Open this publication in new window or tab >>URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E-2-induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats
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2016 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 5, p. 821-828Article in journal (Refereed) Published
Abstract [en]

Objective To determine if inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) can counteract the changes in urodynamic variables and bladder afferent activities induced by intravesical prostaglandin E-2 (PGE(2)) instillation in rats. Materials and methods In female Sprague-Dawley rats we studied the effects of URB937, a peripherally restricted FAAH inhibitor, on single-unit afferent activity (SAA) during PGE(2)-induced bladder overactivity (BO). SAA measurements were made in urethane-anaesthetised rats and Ad-and C-fibres were identified by electrical stimulation of the pelvic nerve and by bladder distention. Cystometry (CMG) in conscious animals and during SAA measurements was performed during intravesical instillation of PGE(2) (50 or 100 mu M) after intravenous administration of URB937 (0.1 and 1 mg/kg) or vehicle. In separate experiments, the comparative expressions of FAAH and cannabinoid receptors, CB1 and CB2, in microsurgically removed L6 dorsal root ganglion (DRG) were studied by immunofluorescence. Results During CMG, 1 mg/kg URB937, but not vehicle or 0.1 mg/kg URB937, counteracted the PGE(2)-induced changes in urodynamic variables. PGE(2) increased the SAAs of C-fibres, but not Ad-fibres. URB937 (1 mg/kg) depressed Ad-fibre SAA and abolished the facilitated C-fibre SAA induced by PGE(2). The DRG nerve cells showed strong staining for FAAH, CB1 and CB2, with a mean (SEM) of 77 (2)% and 87 (3)% of FAAH-positive nerve cell bodies co-expressing CB1 or CB2 immunofluorescence, respectively. Conclusion The present results show that URB937, a peripherally restricted FAAH inhibitor, reduces BO and C-fibre hyperactivity in the rat bladder provoked by PGE(2), suggesting an important role of the peripheral endocannabinoid system in BO and hypersensitivity.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
Keywords
Afferent; endocannabinoids; prostaglandin E-2; Sprague-Dawley rats; urinary bladder
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128139 (URN)10.1111/bju.13223 (DOI)000374282100024 ()26189783 (PubMedID)
Note

Funding Agencies|Ministry of Education, Culture, Sport, Science and Technology of the Japanese Government [40159588, 80595257]; Gester Foundation, Sweden

Available from: 2016-05-19 Created: 2016-05-19 Last updated: 2017-11-30
Hedlund, P. (2015). Editorial Material: Everyday Cold Exposure and Urgency in Translation in EUROPEAN UROLOGY. European Urology, 68(4), 662-663
Open this publication in new window or tab >>Editorial Material: Everyday Cold Exposure and Urgency in Translation in EUROPEAN UROLOGY
2015 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, no 4, p. 662-663Article in journal, Editorial material (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122050 (URN)10.1016/j.eururo.2015.04.011 (DOI)000360573600031 ()25907595 (PubMedID)
Available from: 2015-12-18 Created: 2015-10-19 Last updated: 2017-12-01
Kedia, G. T., Ückert, S., Oelke, M., Sonnenberg, J. E., Sohn, M., Kuczyk, M. A. & Hedlund, P. (2015). Expression and Distribution of Phosphodiesterase Isoenzymes in the Human Male Urethra. Urology, 85(4), 964.e1
Open this publication in new window or tab >>Expression and Distribution of Phosphodiesterase Isoenzymes in the Human Male Urethra
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2015 (English)In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 4, p. 964.e1-Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE To investigate the expression and distribution of phosphodiesterase (PDE) isoenzymes PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A in human urethral tissue. METHODS Specimens of penile urethra were obtained from male subjects who had undergone male-to-female sex reassignment surgery. Using immunohistochemistry (immunofluorescence), the occurrence of PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A, the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide was examined in urethral sections. Cytosolic supernatants prepared from isolated human urethral tissue were subjected to Western blot analysis using specific anti-PDE antibodies. RESULTS Immunosignals specific for PDE1A, 4A, 4B, and 5A were observed in the urethral smooth musculature. The smooth muscle bundles were seen innervated by slender nerve fibers, characterized by the expression of the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. The expression of the PDE isoenzymes mentioned was confirmed by Western blotting. CONCLUSION The results provide evidence for a significance of both the cyclic adenosine monophosphate and cyclic guanosine monophosphate signaling in the control of human urethral smooth muscle. The selective inhibition of PDE isoenzymes might represent a pharmacologic option to influence the function of smooth musculature in the human outflow region.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117375 (URN)10.1016/j.urology.2014.12.030 (DOI)000351944000061 ()25704994 (PubMedID)
Available from: 2015-04-24 Created: 2015-04-24 Last updated: 2017-12-04
Ueckert, S., Sonnenberg, J. E., Albrecht, K., Kuczyk, M. A. & Hedlund, P. (2015). Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human vagina. International journal of impotence research, 27(1), 16-19
Open this publication in new window or tab >>Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human vagina
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2015 (English)In: International journal of impotence research, ISSN 0955-9930, E-ISSN 1476-5489, Vol. 27, no 1, p. 16-19Article in journal (Refereed) Published
Abstract [en]

The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract While the expression of TRPA1 has been investigated in a variety of tissues, up until today no Study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue, Reverse transcriptase PCR (RT-PCR) Was applied in order to identify messenger ribonuleic acid specifically encoding for TAPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of imnnunohistocheitical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences specific for TRPA in the vaginal Wall and epithelium Immunostaining related to TRPA1 was observed in the basal epithelium and in slender Varicose nerve fibers transversing the subepithelial and stromal space of the Vaginal sections. In addition, these fibers presented immunoreactivity specific for nNOS or CGRP The Smooth:musculature of the vaginal wall, and small vessels interspersing the tissue did not present Signals related to TRPA1, The findings indicate that TRPA1 might be involved in afferent neurotransmission in the vagina and work synergistically together with the nitric oxide/cyclic guanosine monophosphate pathway.

Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Hybrid Model Option B, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114434 (URN)10.1038/ijir.2014.23 (DOI)000347660300004 ()25056810 (PubMedID)
Available from: 2015-03-02 Created: 2015-02-20 Last updated: 2017-12-04
Hedlund, P. (2014). Cannabinoids and the Endocannabinoid System in Lower Urinary Tract Function and Dysfunction. Neurourology and Urodynamics, 33(1), 46-53
Open this publication in new window or tab >>Cannabinoids and the Endocannabinoid System in Lower Urinary Tract Function and Dysfunction
2014 (English)In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 33, no 1, p. 46-53Article in journal (Refereed) Published
Abstract [en]

AimsTo review knowledge on cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. MethodsReview of MEDLINE using defined search terms, and manual analysis. Articles published in English were included. Results and DiscussionComponents of the endocannabinoid systemcannabinoid (CB) receptor types 1 and 2, anandamide, and fatty acid amide hydrolase (FAAH), which degrades anandamide and related fatty-acid amideshave been located to lower urinary tract tissues of mice, rats, monkeys, and humans. Studies have located CB receptors in urothelium and sensory nerves and FAAH in the urothelium. CB receptor- and FAAH-related activities have also been reported in the lumbosacral spinal cord. Data on supraspinal CB functions in relation to micturition are lacking. Cannabinoids are reported to reduce sensory activity of isolated tissues, cause antihyperalgesia in animal studies of bladder inflammation, affect urodynamics parameters reflecting sensory functions in animals models, and appear to have effects on storage symptoms in humans. FAAH inhibitors have affected sensory bladder functions and reduced bladder overactivity in rat models. Cannabinoids may modify nerve-mediated functions of isolated lower urinary tract tissues. ConclusionsEvidence suggests components of the endocannabinoid system are involved in regulation of bladder function, possibly at several levels of the micturition pathway. It is unclear if either CB receptor has a dominant role in modification of sensory signals or if differences exist at peripheral and central nervous sites. Amplification of endocannabinoid activity by FAAH inhibitors may be an attractive drug target in specific pathways involved in LUTS.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
Keywords
cannabinoid; cystometry; fatty acid amide hydrolase; receptor; sensation; urinary bladder
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103284 (URN)10.1002/nau.22442 (DOI)000328089600007 ()
Available from: 2014-01-17 Created: 2014-01-16 Last updated: 2017-12-06
Aizawa, N., Hedlund, P., Fuellhase, C., Ito, H., Homma, Y. & Igawa, Y. (2014). Inhibition of Peripheral FAAH Depresses Activities of Bladder Mechanosensitive Nerve Fibers of the Rat. Journal of Urology, 192(3), 956-963
Open this publication in new window or tab >>Inhibition of Peripheral FAAH Depresses Activities of Bladder Mechanosensitive Nerve Fibers of the Rat
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2014 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 3, p. 956-963Article in journal (Refereed) Published
Abstract [en]

Purpose: FAAH degrades endocannabinoids and fatty acid amides. FAAH inhibition reduces micturition frequency and counteracts bladder overactivity in rats. We studied the effects of the peripherally active selective FAAH inhibitor URB937, and the CB1 and CB2 receptor antagonists rimonabant and SR144528, respectively, on single unit afferent activity of primary bladder afferents in rats. Materials and Methods: Female Sprague Dawley (R) rats were anesthetized. Single unit afferent activity of A delta or C-fibers from the L6 dorsal roots was recorded during bladder filling before and after URB937 administration with or without rimonabant or SR144528. Drugs (1 mg/kg) were given intravenously. FAAH, CB1 and CB2 expression, and expression of the sensory marker CGRP in the L6 dorsal root ganglion were compared by immunofluorescence. Results: A total of 102 single afferent fibers (48 A delta and 54 C-fibers) were isolated from 57 rats. URB937 decreased single unit afferent activity of C-fibers to a mean +/- SEM of 78% +/- 9% and of A delta-fibers to a mean of 67% +/- 7% while increasing bladder compliance to a mean of 116% +/- 3%. The effects of URB937 on single unit afferent activity and bladder compliance were counteracted by rimonabant or SR144528. Rimonabant increased single unit afferent activity of each fiber type but SR144528 affected only A delta-fiber activity. CGRP positive L6 dorsal root ganglion neurons showed strong FAAH, CB1 and CB2 staining. Conclusions: To our knowledge we report for the first time that inhibiting peripheral FAAH depresses the Ad and C-fiber activity of primary bladder afferents via CB1 and CB2 receptors. CB antagonists alone exerted facilitatory effects on single unit afferent activity during bladder filling in rats. The endocannabinoid system may be involved in physiological control of micturition as regulators of afferent signals.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
urinary bladder; endocannabinoids; nerves, afferent; urination; receptors, cannabinoid
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-111459 (URN)10.1016/j.juro.2014.04.008 (DOI)000342105600110 ()24746881 (PubMedID)
Note

Funding Agencies|Ministry of Education, Culture, Sport, Science and Technology of the Japanese Government [40159588, 80595257]; Shimabara Science Promotion Foundation, Tokyo, Japan; Gester Foundation, Helsingborg, Sweden

Available from: 2014-10-21 Created: 2014-10-17 Last updated: 2017-12-05
Abrate, A., Buono, R., Canu, T., Esposito, A., Del Maschio, A., Luciano, R., . . . Cavarretta, I. T. R. (2014). Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression. European Journal of Cancer, 50(14), 2478-2488
Open this publication in new window or tab >>Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression
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2014 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no 14, p. 2478-2488Article in journal (Refereed) Published
Abstract [en]

Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase:: uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Mesenchymal stem cells; Prodrug activating enzymes; Prostate cancer; TRAMP mice; Magnetic resonance imaging
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-111273 (URN)10.1016/j.ejca.2014.06.014 (DOI)000341449200012 ()25060826 (PubMedID)
Note

Funding Agencies|Sanofi; Associazione Amici di URI onlus; Slovak League against Cancer

Available from: 2014-10-14 Created: 2014-10-14 Last updated: 2017-12-05
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