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1.
Sci Rep ; 8(1): 15102, 2018 10 10.
Article in English | MEDLINE | ID: mdl-30305693

ABSTRACT

The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.


Subject(s)
Immunomodulation , Immunotherapy , Nontuberculous Mycobacteria/immunology , Urinary Bladder Neoplasms/immunology , Administration, Intravesical , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , BCG Vaccine , Biomarkers , Cell Line, Tumor , Disease Models, Animal , Immunotherapy/methods , Mice , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/therapy
2.
Nat Prod Res ; 31(5): 515-522, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27266725

ABSTRACT

Schizogyne sericea, well-known as 'salado', is a halophytic shrub widespread on coastal rocks of Tenerife (Canary Islands). This plant is used traditionally as analgesic, astringent, anti-inflammatory and vulnerary agent. In the present work, we have analysed the aqueous and ethanolic extracts of S. sericea for the content of phenolic acids by HPLC-DAD. The dynamic solid-liquid Naviglio® extractor was used to extract the flowering aerial parts. Aqueous extracts showed higher levels of phenolics than ethanolic extracts. S. sericea extracts were rich in chlorogenic and isochlorogenic acids. The Naviglio® extracts obtained were assayed for in vitro biological activities, namely antioxidant, antimicrobial and cytotoxicity on tumour cells by DPPH, ABTS, FRAP, agar disc-diffusion and MTT methods, respectively. Results showed that aqueous extracts, being richer in phenolic acids, are endowed with relevant radical scavenging activity (TEAC values in the range 208-960 µmol TE/g) while ethanolic extracts exhibited noteworthy antiproliferative effects on tumour cells.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Asteraceae/chemistry , Hydroxybenzoates/analysis , Plant Extracts/pharmacology , Cell Line, Tumor , Humans
3.
Chem Biodivers ; 13(7): 826-36, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27272544

ABSTRACT

Schizogyne sericea (Asteraceae) is a halophytic shrub endemic to the Canary Islands and traditionally employed as analgesic, astringent, anti-inflammatory, and vulnerary. A comprehensive phytochemical investigation was conducted on the flowering aerial parts by analyzing both essential oil constituents and polar compounds. The essential oil was dominated by p-cymene, with the noteworthy occurrence of ß-pinene and thymol esters. From the EtOH extract, eight compounds were isolated and structurally elucidated. Essential oil, polar fractions, and isolates (2), (4), and (5) were separately in vitro assayed for antiproliferative activity on human tumor cell lines (A375, MDA-MB 231, and HCT116) by MTT assay, for antioxidant potential by DPPH, ABTS, and FRAP assays, and for antimicrobial activity by the agar disk diffusion method. Results revealed that essential oil and compounds 1 and 2 exert a strong inhibition on tumor cells, and in some cases, higher than that of cisplatin. Fractions containing thymol derivatives (1 and 2) and caffeoylquinic acid derivatives 4 and 5 displayed antioxidant activity comparable to that of Trolox, making S. sericea extract an interesting natural product with potential applications as preservative or in the treatment of diseases in which oxidative stress plays an important role.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Asteraceae/chemistry , Asteraceae/metabolism , Oils, Volatile/pharmacology , Phenols/pharmacology , Secondary Metabolism , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/metabolism , Antifungal Agents/analysis , Antifungal Agents/metabolism , Antineoplastic Agents, Phytogenic/analysis , Antineoplastic Agents, Phytogenic/metabolism , Antioxidants/analysis , Antioxidants/metabolism , Bacteria/drug effects , Bacteria/growth & development , Candida albicans/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Humans , Microbial Sensitivity Tests , Molecular Structure , Oils, Volatile/analysis , Oils, Volatile/metabolism , Phenols/analysis , Phenols/metabolism , Spain , Structure-Activity Relationship
4.
Eur Urol Focus ; 2(1): 67-76, 2016 Apr.
Article in English | MEDLINE | ID: mdl-28723453

ABSTRACT

BACKGROUND: Bacillus Calmette-Guérin (BCG) prevents tumour recurrence and progression in non-muscle-invasive bladder cancer (BC). However, common adverse events occur, including BCG infections. OBJECTIVE: To find a mycobacterium with similar or superior antitumour activity to BCG but with greater safety. DESIGN: In vitro, ex vivo, and in vivo comparisons of the antitumour efficacy of nonpathogenic mycobacteria and BCG. INTERVENTION: The in vitro antitumour activity of a broad set of mycobacteria was studied in seven different BC cell lines. The most efficacious was selected and its ex vivo capacity to activate immune cells and its in vivo antitumour activity in an orthotopic murine model of BC were investigated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Growth inhibition of BC cells was the primary outcome measurement. Parametric and nonparametric tests were use to analyse the in vitro results, and a Kaplan-Meier test was applied to measure survival in mycobacteria-treated tumour-bearing mice. RESULTS AND LIMITATIONS: Mycobacterium brumae is superior to BCG in inhibiting low-grade BC cell growth, and has similar effects to BCG against high-grade cells. M. brumae triggers an indirect antitumour response by activating macrophages and the cytotoxic activity of peripheral blood cells against BC cells. Although no significant differences were observed between BCG and M. brumae treatments in mice, M. brumae treatment prolonged survival in comparison to BCG treatment in tumour-bearing mice. In contrast to BCG, M. brumae does not persist intracellularly or in tumour-bearing mice, so the risk of infection is lower. CONCLUSIONS: Our preclinical data suggest that M. brumae represents a safe and efficacious candidate as a therapeutic agent for non-muscle-invasive BC. PATIENT SUMMARY: We investigated the antitumour activity of nonpathogenic mycobacteria in in vitro and in vivo models of non-muscle-invasive bladder cancer. We found that Mycobacterium brumae effectively inhibits bladder cancer growth and helps the host immune system to eradicate cancer cells, and is a promising agent for antitumour immunotherapy.

5.
Nat Prod Res ; 29(17): 1641-9, 2015.
Article in English | MEDLINE | ID: mdl-25560780

ABSTRACT

Cedronella canariensis is a lemon-scented species of the family Lamiaceae endemic to the Canary Islands where it is used in the traditional medicine to prepare infusions or inhalations for anti-catarrhal, tonic, diuretic, hypoglycaemiant, hypotensive, anti-inflammatory and decongestant of the respiratory tract. In this work we investigated for the first time the antioxidant activity of the essential oil and its inhibitory effects on tumour cells (A375, MDA-MB-231, HCT 116) proliferation by DPPH, ABTS, FRAP and MTT assays, respectively. The oil, analysed by GC-ionisation flame detector and GC-MS, was characterised by pinocarvone (58.0%) and ß-pinene (10.8%) as the major constituents, being typical of the chemotype 'canariensis'. Noteworthy was the cytotoxic activity of the oil against the tumour cells examined, with IC50 values of 4.3, 7.3 and 11.4 µg/mL on A375, MDA-MB-231 and HCT 116 tumour cells, respectively, as well as the scavenging activity against the ABTS radical (IC50 of 10.5 µg/mL).


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Free Radical Scavengers/pharmacology , Lamiaceae/chemistry , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Bicyclic Monoterpenes , Bridged Bicyclo Compounds/pharmacology , Cell Line, Tumor/drug effects , Gas Chromatography-Mass Spectrometry , HCT116 Cells/drug effects , Humans , Monoterpenes/pharmacology , Spain
6.
Fitoterapia ; 100: 95-109, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25464055

ABSTRACT

In the present work we carried out a phytochemical and biological investigation on three Hypericum species, i.e. Hypericum reflexum, Hypericum canariense and Hypericum grandifolium, from the Canary Islands where they are traditionally used as diuretic, wound healing, vermifuge, sedative and antidepressive agents. The polar extracts of the top flowering aerial parts, prepared by Soxhlet apparatus using a methanol-acetone (1:1) extracting mixture, were analyzed by HPLC-DAD and HPLC-MS for the content of eight biomarkers such as hypericin, hyperforin, chlorogenic acid, rutin, hyperoside, isoquercitrin, quercitrin and quercetin, whereas the hydrodistilled essential oils were analyzed by GC-FID and GC-MS. The three Hypericum species had different results in both polar and volatile constituents, H. reflexum being the only one endowed with a small amount of naphtodianthrones (hypericin and pseudohypericin), and containing high levels of chlorogenic acid, rutin and volatile mono- and sesquiterpenes. After chemical characterization, all products were in vitro biologically assayed for antiproliferative activity on human tumor cell lines by MTT assay, for antioxidant potential by DPPH, ABTS and FRAP assays, and for antimicrobial activity by the agar disc diffusion and microdilution methods. Results revealed interesting bioactivities and differences between polar extracts and essential oils, with the former being endowed with significant antioxidant activity and the latter with comparable inhibition effects on the tumor cells (A375, MDA-MB 231 and HCT 116) to that of cisplatin.


Subject(s)
Hypericum/chemistry , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Plant Components, Aerial/chemistry , Plant Extracts/chemistry , Spain
7.
N Biotechnol ; 31(5): 492-8, 2014 Sep 25.
Article in English | MEDLINE | ID: mdl-25063342

ABSTRACT

Regenerative therapies using adult stem cells have attracted great interest in the recent years and offer a promising alternative to current surgical practices. In this report, we evaluated the safety and efficacy of an autologous cell-based treatment of osteoarthritis using mesenchymal stromal cells expanded from bone marrow aspirates that were administered intra-articularly. Ten 2-year old ewes were divided in two groups (for analysis at 6 and 12 months, respectively). Full thickness articular cartilage defects of approximately 60mm(2) were created arthroscopically in the medial femorotibial condyles and a meniscal tear in the anterior horn of the medial meniscus in the 20 hind legs. Intra-articular injection of 4 mL of either treatment (a suspension of cells) or control (same as treatment, without cells) were applied one month after generating a chronic condition similar to human pathology. Animals were monitored radiographically, by MRI and ultrasound scanning; and macroscopic and histological analyses were conducted at 6 and 12 months. Furthermore a full necropsy was performed at 12 months post-treatment. The intra-articular injection of autologous MSC was safe, as judged by the lack of local or systemic adverse effects during the clinical follow-up and by a full necropsy performed at 12 months post-treatment. Evidence of regeneration of articular cartilage and meniscus was case-dependent but statistically significant improvement was found in specific macroscopic and histological parameters. Such parameters included colour, rigidity, cell distribution and hyaline quality of the refill tissue as well as the structure of subchondral bone.


Subject(s)
Cartilage, Articular/injuries , Knee Injuries/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Tibial Meniscus Injuries , Animals , Autografts , Cartilage, Articular/diagnostic imaging , Chronic Disease , Disease Models, Animal , Humans , Knee Injuries/diagnostic imaging , Magnetic Resonance Imaging , Menisci, Tibial/diagnostic imaging , Radiography , Sheep
8.
Genes Dev ; 27(6): 639-53, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23468428

ABSTRACT

The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1-3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle.


Subject(s)
Cell Cycle/physiology , Genomic Instability , Sirtuin 2/metabolism , Acetylation , Amino Acid Sequence , Animals , Cell Transformation, Neoplastic/genetics , Chromatin/metabolism , DNA Damage/genetics , Gene Knockout Techniques , HeLa Cells , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Humans , M Phase Cell Cycle Checkpoints/physiology , Methylation , Mice , Mice, Knockout , Mitosis , Protein Binding , Sirtuin 2/genetics
9.
Am J Vet Res ; 72(8): 1087-96, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21801067

ABSTRACT

OBJECTIVE: To evaluate expression of matrix metalloproteinase (MMP)-2 and -9 and membrane-type 1 MMP (MT1-MMP) in melanocytomas and malignant melanomas of dogs, analyze in vitro production of MMPs by canine melanoma cell lines and primary dermal fibroblasts, and investigate mutual communication between tumor cells and fibroblasts and the influence of collagen on MMP regulation. SAMPLE: 35 biopsy specimens from melanocytic tumors and primary dermal fibroblasts of dogs and 3 canine melanoma cell lines (CML-1, CML-10c2, and CML-6M). PROCEDURES: MMP-2, MMP-9, and MT1-MMP were detected in tumor samples by use of immunohistochemical analysis. In vitro production was analyzed via reverse transcriptase-PCR assay, immunocytochemical analysis, zymography, and immunoblotting. RESULTS: MMP-9 was overexpressed in malignant melanomas, compared with expression in melanocytomas, whereas no significant differences in MMP-2 and MT1-MMP immunostaining were detected. Stromal cells also often had positive staining results. In vitro, all 3 melanoma cell lines and dermal fibroblasts had evidence of MMP-2 and MT1-MMP, but only melanoma cells had evidence of MMP-9. Coculture of CML-1 or CML-10c2 cells and dermal fibroblasts induced an increase in expression of the active form of MMP-2. Culture of melanoma cells on type I collagen increased the activation state of MT1-MMP. CONCLUSIONS AND CLINICAL RELEVANCE: MMP-9 expression was increased in malignant melanomas of dogs. Stromal cells were a source for MMPs. Stromal cells, in combination with matrix components such as type I collagen, can interact with tumor cells to regulate MMP production. Information about MMP production and regulation could help in the development of new treatments.


Subject(s)
Dog Diseases/enzymology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinases/metabolism , Melanoma/veterinary , Skin Neoplasms/veterinary , Animals , Cell Line , Cells, Cultured , Dog Diseases/pathology , Dogs , Fibroblasts/enzymology , Fibroblasts/pathology , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Hyaluronan Receptors/analysis , Hyaluronan Receptors/metabolism , Hyaluronic Acid/analysis , Hyaluronic Acid/metabolism , Immunoenzyme Techniques/veterinary , Matrix Metalloproteinase 14/analysis , Matrix Metalloproteinase 14/metabolism , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinases/analysis , Melanoma/enzymology , Melanoma/pathology , Skin/enzymology , Skin/pathology , Skin Neoplasms/enzymology , Skin Neoplasms/pathology
10.
Muscle Nerve ; 41(5): 630-41, 2010 May.
Article in English | MEDLINE | ID: mdl-19918773

ABSTRACT

Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy.


Subject(s)
Diabetic Neuropathies/immunology , Diabetic Neuropathies/physiopathology , Insulin-Secreting Cells/immunology , Interferon-beta/metabolism , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , Animals , Diabetes Mellitus, Experimental/complications , Diabetic Neuropathies/pathology , Disease Models, Animal , Electrophysiology , Humans , Insulin-Secreting Cells/metabolism , Interferon-beta/genetics , Male , Mice , Mice, Inbred ICR , Mice, Transgenic , Nerve Regeneration/physiology , Neural Conduction/physiology , Promoter Regions, Genetic/genetics , Rats , Sciatic Neuropathy/immunology , Sciatic Neuropathy/pathology , Sciatic Neuropathy/physiopathology , Sensory Receptor Cells/immunology , Sensory Receptor Cells/pathology , Somatosensory Disorders/diagnosis , Somatosensory Disorders/physiopathology , Streptozocin/pharmacology , Wallerian Degeneration/immunology , Wallerian Degeneration/pathology , Wallerian Degeneration/physiopathology
11.
Eur J Nucl Med Mol Imaging ; 36(7): 1156-66, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19252908

ABSTRACT

PURPOSE: The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. METHODS: Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. RESULTS: Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal--but not acinar--tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. CONCLUSION: In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours.


Subject(s)
Carcinoma, Acinar Cell/diagnostic imaging , Carcinoma, Acinar Cell/metabolism , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/metabolism , Fluorodeoxyglucose F18/metabolism , Genes, myc , Animals , Carcinoma, Acinar Cell/enzymology , Carcinoma, Acinar Cell/genetics , Carcinoma, Pancreatic Ductal/enzymology , Carcinoma, Pancreatic Ductal/genetics , Elongin , Female , Gene Expression Regulation, Neoplastic , Glucose Transport Proteins, Facilitative/genetics , Hexokinase/genetics , Male , Mice , Mice, Transgenic , Positron-Emission Tomography , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Factors/genetics
12.
Am J Vet Res ; 68(12): 1376-85, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18052744

ABSTRACT

OBJECTIVE: To analyze the expression of versican and hyaluronan in melanocytomas and malignant melanomas of dogs, to correlate their expression with expression of the hyaluronan receptor CD44, and to identify enzymes responsible for the synthesis and degradation of hyaluronan in canine dermal fibroblasts and canine melanoma cell lines. SAMPLE POPULATION: 35 biopsy specimens from melanocytic tumors of dogs, canine primary dermal fibroblasts, and 3 canine melanoma cell lines. PROCEDURES: Versican, hyaluronan, and CD44 were detected in tumor samples by use of histochemical or immunohistochemical methods. Expression of hyaluronan-metabolizing enzymes was analyzed with a reverse transcriptase-PCR assay. RESULTS: Versican was found only in some hair follicles and around some blood vessels in normal canine skin, whereas hyaluronan was primarily found within the dermis. Hyaluronan was found in connective tissue of the oral mucosa. Versican and, to a lesser extent, hyaluronan were significantly overexpressed in malignant melanomas, compared with expression in melanocytomas. No significant difference was found between malignant tumors from oral or cutaneous origin. The expression of both molecules was correlated, but hyaluronan had a more extensive distribution than versican. Versican and hyaluronan were mainly associated with tumor stroma. Canine fibroblasts and melanoma cell lines expressed hyaluronan synthase 2 and 3 (but not 1) and hyaluronidase 1 and 2. CONCLUSIONS AND CLINICAL RELEVANCE: Versican may be useful as a diagnostic marker for melanocytic tumors in dogs. Knowledge of the enzymes involved in hyaluronan metabolism could reveal new potential therapeutic targets.


Subject(s)
Dog Diseases/metabolism , Hyaluronic Acid/metabolism , Melanoma/veterinary , Versicans/metabolism , Animals , Cell Line, Tumor , Dogs , Fibroblasts/metabolism , Gene Expression Regulation, Neoplastic , Hyaluronan Receptors/metabolism , Hyaluronic Acid/genetics , Isoenzymes , Melanoma/metabolism , Versicans/genetics
13.
Vet Dermatol ; 17(6): 449-52, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17083578

ABSTRACT

A case of a dwarf hamster with two progressively growing nodules on the right fore limb is described. These were excised following ineffective medical treatment and were submitted for histopathological examination, which revealed bacterial pseudomycetoma in both nodules. To the authors' knowledge this is the first reported case of bacterial pseudomycetoma in a dwarf hamster.


Subject(s)
Cricetinae , Gram-Positive Bacterial Infections/veterinary , Gram-Positive Cocci/isolation & purification , Mycetoma/veterinary , Rodent Diseases/diagnosis , Animals , Diagnosis, Differential , Forelimb , Gram-Positive Bacterial Infections/diagnosis , Male , Mycetoma/diagnosis , Rodent Diseases/microbiology , Rodent Diseases/pathology , Rodent Diseases/surgery
14.
Lab Invest ; 86(9): 889-901, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16847433

ABSTRACT

Versican is a large chondroitin sulfate proteoglycan produced by several tumor cell types, including malignant melanoma, which exists as four different splice variants. The presence of versican in the extracellular matrix plays a role in tumor cell growth, adhesion and migration, which could be altered by altering the ratio between versican isoforms. We have previously shown that overexpression of the V3 isoform of versican in human melanoma cell lines markedly reduces cell growth in vitro and in vivo, since V3-overexpressing (LV3SN) cultured cells as well as primary tumors arising from these cells grow slower than their vector-only counterparts (LXSN). In the present work, we have extended these observations to demonstrate that the delayed cell growth is due to multiple events since differences in proliferative index as well as in apoptosis are observed in LV3SN cells and tumors compared to LXSN. For example, LV3SN melanoma cells exhibit delayed activation of MAPK in response to EGF, we have also characterized further the primary tumors originated in nude mice from V3-transduced melanoma cells to determine if other events affect the V3 tumor phenotype. For example, hyaluronan content of LV3SN tumors was higher than in LXSN tumors, whereas other related matrix components and vascularization were unaffected. Furthermore, lung metastasis in nude mice occurred only in animals carrying LV3SN tumors, indicating a dual role for this molecule, both as an inhibitor of tumor growth and a metastasis inductor.


Subject(s)
Chondroitin Sulfate Proteoglycans/metabolism , Lectins, C-Type/metabolism , Melanoma/metabolism , Proteoglycans/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Melanoma/pathology , Neoplasm Invasiveness , Protein Isoforms/metabolism , Versicans
15.
Phytother Res ; 16(8): 740-4, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12458477

ABSTRACT

The infusions of the aerial parts in blossom of Hypericum canariense, H. glandulosum, H. reflexum and H. grandifolium (Hypericaceae) were evaluated for their pharmacological activity on the central nervous system in mice using various behavioural models including locomotor and muscle relaxant activity, effect on normal body temperature, pentobarbital-induced sleep, oxotremorine and tetrabenazine-induced syndrome, apomorphine-induced hypothermia and 5-hydroxytryptophan-induced head twitches, as well as a forced swimming test. These infusions did not alter significantly the locomotor activity, pentobarbital induced sleeping time and body temperature, with the exception of H. canariense which produced a slight but significant hypothermia. Additionally, no muscle relaxant or anticholinergic activity were observed. These infusions antagonized the ptosis and/or motor depression induced by tetrabenazine as well as shortening the immobility time in the forced swimming test. The observations suggest that the infusions of these Hypericum species possess antidepressant activity in mice, without inducing muscle relaxation, anticholinergic and sedative properties.


Subject(s)
Antidepressive Agents/pharmacology , Central Nervous System/drug effects , Hypericum , Motor Activity/drug effects , Phytotherapy , Plant Extracts/pharmacology , Administration, Oral , Animals , Antidepressive Agents/administration & dosage , Antidepressive Agents/chemistry , Antidepressive Agents/therapeutic use , Apomorphine , Body Temperature/drug effects , Female , Flowering Tops , Hypericum/classification , Indian Ocean Islands , Lethal Dose 50 , Male , Mice , Pentobarbital , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Plant Extracts/toxicity , Random Allocation , Sleep/drug effects
16.
Am J Vet Res ; 63(9): 1257-61, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12224856

ABSTRACT

OBJECTIVE: To evaluate molecular abnormalities in the c-kit gene of canine mast cell tumors (MCT) with different grades of cellular differentiation. SAMPLE POPULATION: 31 normal tissue specimens from dogs and 45 canine MCT classified according to grade of cell differentiation. PROCEDURES: Genomic DNA extractions were made from canine MCT and normal tissues. Parts of exon 11, intron 11, and exon 12 of the c-kit gene were amplified by use of polymerase chain reaction. These regions were cloned, sequenced, and compared with GenBank sequences of the National Center for Biotechnology International. A statistical analysis was used to compare sequences from canine MCT and normal tissues. RESULTS: A significantly higher percentage of homozygous intron 11 deletion was found in canine MCT (49%) than in normal tissues (13%). This percentage was also higher in moderately and poorly differentiated MCT, compared with well-differentiated MCT Although no mutations were detected in any of the specimens, a polymorphism at amino acid position 606 of the canine c-kit sequence was found in all the studied sequences. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a relationship between intron 11 deletion and MCT and the grade of MCT differentiation. We suggest that intron 11 deletion may be implicated in the pathogenesis of MCT and could be used as a marker for diagnosis and prognosis of canine MCT.


Subject(s)
Introns/genetics , Mastocytoma/genetics , Mastocytoma/veterinary , Neoplasms/genetics , Neoplasms/veterinary , Proto-Oncogene Proteins c-kit/genetics , Sequence Deletion/genetics , Animals , Base Sequence , DNA Mutational Analysis , Dog Diseases/genetics , Dogs , Molecular Sequence Data
17.
J Ethnopharmacol ; 81(1): 43-7, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12020926

ABSTRACT

A previous chemical study of Sideritis canariensis var. pannosa demonstrated the presence of some important classes of related organic compounds with anti-inflammatory activities. In the present study, the crude ethanol extract and the chloroformic and aqueous fractions of S. canariensis have been examined for their antimicrobial actions through the disk-diffusion method and for their anti-inflammatory and analgesic effects in several animal models. No relevant antimicrobial activity against the tested microorganisms was found. The chloroformic fraction was the most interesting, exhibiting a good analgesic and anti-inflammatory activity.


Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , Pain/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Sideritis , Acetic Acid/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carrageenan/pharmacology , Chloroform , Diffusion , Disease Models, Animal , Edema/drug therapy , Ethanol , Female , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Inflammation/chemically induced , Male , Mice , Pain/chemically induced , Plant Components, Aerial
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