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1.
Ann Ig ; 26(3): 213-8, 2014.
Article in English | MEDLINE | ID: mdl-24998212

ABSTRACT

The goal of the study was to observe the opinion of the GPs of one of the two Turin Local Health Unit (from now on LHU) and compare them to what emerges from literature. We employed a questionnaire administered via phone to all the 389 GPs active in the LHU in October 2013. The percentage of responders was 81.5%. Among the responders, 95% are in favor of acupuncture, 84.2% believe that it is scientifically based, 6% practice acupuncture, 25.2% use it on themselves, and 66.2% have sent at least one patient to an acupuncturist in the last year. 82% of responders are in favour of adding acupuncture training to their own professional practice, and 71.9% believe it would be useful to include acupuncture in specific training for general practice. 64% believe that acupuncture should be included into the benefits offered by the NHS. Data show that interest for acupuncture is higher than that observed in previous international studies carried out on the same topics in the last 20 years; in our opinion, such an increase in confidence and trust in acupuncture is due to the skilled performance offered by the public service in this LHU, which is also guaranteed by a prestigious acupuncture school.


Subject(s)
Acupuncture Therapy/statistics & numerical data , Attitude of Health Personnel , General Practice/statistics & numerical data , General Practitioners/statistics & numerical data , Adult , Aged , Female , General Practice/methods , General Practitioners/psychology , Humans , Italy , Male , Middle Aged , National Health Programs , Practice Patterns, Physicians'/statistics & numerical data , Surveys and Questionnaires
2.
Eur Respir J ; 32(2): 443-51, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18385176

ABSTRACT

Human malignant mesothelioma (HMM), which is strongly related to asbestos exposure, exhibits high resistance to many anticancer drugs. Asbestos fibre deposition in the lung may cause hypoxia and iron chelation at the fibre surface. Hypoxia-inducible factor (HIF)-1alpha, which is upregulated by a decreased availability of oxygen and iron, controls the expression of membrane transporters, such as P-glycoprotein (Pgp), which actively extrude the anticancer drugs. The present study aimed to assess whether asbestos may play a role in the induction of doxorubicin resistance in HMM cells through the activation of HIF-1alpha and an increased expression of Pgp. After 24-h incubation with crocidolite asbestos or with the iron chelator dexrazoxane, or under hypoxia, HMM cells were tested for HIF-1alpha activation, Pgp expression, accumulation of doxorubicin and sensitivity to its toxic effect. Crocidolite, dexrazoxane and hypoxia caused HIF-1alpha activation, Pgp overexpression and increased resistance to doxorubicin accumulation and toxicity. These effects were prevented by the co-incubation with the cell-permeating iron salt ferric nitrilotriacetate, which caused an increase of intracellular iron bioavailability, measured as increased activity of the iron regulatory protein-1. Crocidolite, dexrazoxane and hypoxia induce doxorubicin resistance in human malignant mesothelioma cells by increasing hypoxia-inducible factor-1alpha activity, through an iron-sensitive mechanism.


Subject(s)
Asbestos/toxicity , Drug Resistance, Neoplasm , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents/pharmacology , Asbestos, Crocidolite/pharmacology , Cell Line, Tumor , Doxorubicin/pharmacology , Humans , Hypoxia , Iron/metabolism , Lung/pathology , Razoxane/pharmacology
3.
Pediatr Hematol Oncol ; 20(8): 583-8, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14578027

ABSTRACT

Secondary malignancies are a well-known late complication occurring in patients who undergo bone marrow transplant (BMT) during childhood. A boy with acute lymphoblastic leukemia experienced a BM relapse at the age of 14 years and underwent an autologous BMT conditioned with TBI and melphalan. Sixteen years later a malignant mesothelioma of the peritoneum was diagnosed. A surgical approach according to the Sugarbaker technique and hyperthermic peritoneal perfusion with CDDP and Adriamycin were performed. The patient is alive and well after a follow-up of 20 months. To the authors' knowledge this is the first case of mesothelioma as a secondary malignancy after BMT.


Subject(s)
Abdominal Neoplasms/etiology , Bone Marrow Transplantation/adverse effects , Mesothelioma/etiology , Adolescent , Humans , Male , Mesothelioma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Transplantation, Autologous
5.
J Pathol ; 193(4): 468-75, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11276005

ABSTRACT

Vascular endothelial growth factor (VEGF), a potent mitogen for vascular endothelium, is expressed in malignant pleural mesothelioma (MM). The present report examines the effect of VEGF on MM growth. Four MM cell lines produced significantly higher VEGF levels than normal mesothelial cells (1946+/-14 pg/ml vs. 180+/-17 pg/ml; p<0.001). In addition, MM cells expressed the tyrosine kinase-related VEGF receptors Flt-1 and KDR. Recombinant human VEGF phosphorylated both Flt-1 and KDR and increased proliferation of all four MM cell lines in a dose-dependent fashion. Neutralizing antibodies against either VEGF, Flt-1 or KDR significantly reduced MM cellular proliferation. In addition, expression of VEGF, Flt-1, and KDR was observed in MM biopsies. Moreover, higher VEGF levels were found in the pleural effusions of MM patients than in the effusions of patients with non-malignant pleural disease (1885.7+/-894.9 pg/ml vs. 266.9+/-180.5 pg/ml; p<0.001). Linear regression analysis showed a significant inverse correlation between serum VEGF levels and MM patient survival (r=0.72; p<0.01). No correlation was found between tumour vessel density and either serum (r=0.26; p=0.42) or pleural effusion (r=0.35; p=0.26) VEGF levels. These results indicate that VEGF, via activation of its tyrosine kinase receptors, may be a key regulator of MM growth. In addition, VEGF production could have an impact on patient survival, not only by promoting tumour angiogenesis but also by directly stimulating tumour growth.


Subject(s)
Autocrine Communication/physiology , Biomarkers, Tumor/metabolism , Endothelial Growth Factors/metabolism , Lymphokines/metabolism , Mesothelioma/metabolism , Pleural Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Cell Division/drug effects , Dose-Response Relationship, Drug , Endothelial Growth Factors/pharmacology , Extracellular Matrix Proteins/metabolism , Female , Humans , Lymphokines/pharmacology , Male , Mesothelioma/blood supply , Middle Aged , Neovascularization, Pathologic/pathology , Phosphorylation/drug effects , Pleural Effusion, Malignant/metabolism , Pleural Neoplasms/blood supply , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Growth Factor/metabolism , Receptors, Vascular Endothelial Growth Factor , Recombinant Proteins/pharmacology , Retrospective Studies , Survival Rate , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-1 , Vascular Endothelial Growth Factors
6.
Oncogene ; 19(45): 5208-11, 2000 Oct 26.
Article in English | MEDLINE | ID: mdl-11064459

ABSTRACT

Oncogenic activation of the Ron tyrosine kinase (Macrophage Stimulating Protein receptor) relies on substitutions of two highly conserved residues in the catalytic domain (D1232V and M1254T), which result in ligand-independent activation of the receptor, in vivo tumorigenesis and metastasis. We show here that the Y/F conversion of the Y1317 residue in the kinase domain impairs tumorigenic and metastatic properties of Ron activated by the MEN2B-like mutation (RonM1254T), but not by other two oncogenic substitutions. Furthermore, RonM1254T lacking the multifunctional docking site retains transforming and metastatic activity. These data reveal that the transforming activity of RonM1254T mutant is dependent on Y1317 phosphorylation, suggesting a shift in intramolecular substrate specificity. Consistently, a shift of RonM1254T kinase substrate specificity was observed by in vitro peptide phosphorylation assays and in vivo receptor auto-phosphorylation. The Y1317 phosphorylation elicits by itself activation of PI-3K/Akt and MAPK signalling pathways. Our data indicate that the accomplishment of the full oncogenic phenotype of RonM1254T requires the phosphorylation both of the canonical C-terminal docking site and of the unique Y1317 residue in the tyrosine kinase domain.


Subject(s)
Cell Transformation, Neoplastic/genetics , Protein Serine-Threonine Kinases , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Cell Surface/genetics , Mitogen-Activated Protein Kinases/metabolism , Multiple Endocrine Neoplasia Type 2b/genetics , Mutation , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-akt , Receptor, ErbB-2/genetics , Recombinant Fusion Proteins , Signal Transduction , Substrate Specificity
7.
Vaccine ; 19(1): 10-5, 2000 Aug 15.
Article in English | MEDLINE | ID: mdl-10924781

ABSTRACT

A total of 242 healthy adults were immunised with a first dose of an investigational inactivated hepatitis A vaccine. Three concentrations (3, 6 and 12 EU [ELISA units]) of the experimental vaccine were used and compared to a licensed reference vaccine. The aim was to determine the antigenic concentration of the study vaccine inducing the highest seroconversion rate and anti-Hepatitis A virus (HAV) antibody response at 2 weeks after the primary immunisation. A booster dose was given at month 6. At 15 days after the primary immunisation the seroconversion rates in subjects vaccinated with the 6 and 12 EU vaccines were 78 and 94%, respectively. At 30 and 180 days after the primary immunisation the percentages of seropositivity were 100% for both groups. The antibody response to the 12 EU study vaccine was similar to that to the reference vaccine. The percentages of seropositivity at 15 and 180 days after the primary immunisation were 94 vs 93%, and 100 vs 93% in the experimental and reference vaccine respectively. Thus, because it induces early and lasting seroconversion, the 12 EU study vaccine seems to be the most effective as a high potency HAV vaccine.


Subject(s)
Hepatitis Antibodies/blood , Vaccines, Inactivated/administration & dosage , Viral Hepatitis Vaccines/administration & dosage , Adolescent , Adult , Demography , Double-Blind Method , Female , Hepatitis A Antibodies , Hepatitis A Vaccines , Humans , Immunity/drug effects , Immunization, Secondary , Male , Vaccines, Inactivated/adverse effects , Viral Hepatitis Vaccines/adverse effects
8.
Oncogene ; 17(6): 741-9, 1998 Aug 13.
Article in English | MEDLINE | ID: mdl-9715276

ABSTRACT

Ron (the receptor for Macrophage Stimulating Protein) has never been implicated before in human malignancies or in cell transformation. In this report we show that Ron can acquire oncogenic potential by means of two amino acid substitutions-D1232V and M1254T-affecting highly conserved residues in the tyrosine kinase domain. The same mutations in Kit and Ret have been found associated with two human malignancies, mastocytosis and Multiple Endocrine Neoplasia type 2B (MEN2B), respectively. Both mutations caused Ron-mediated transformation of 3T3 fibroblasts and tumour formation in nude mice. Moreover, cells transformed by the oncogenic Ron mutants displayed high metastatic potential. The Ron mutant receptors were constitutively active and the catalytic efficiency of the mutated kinase was higher than that of wild-type Ron. Oncogenic Ron mutants enhanced activation of the Ras/MAPK cascade with respect to wild type Ron, without affecting the JNK/SAPK pathway. Expression of Ron mutants in 3T3 fibroblasts led to different patterns of tyrosine-phos-phorylated proteins. These data show that point mutations altering catalytic properties and possibly substrate specificity of the Ron kinase may force cells toward tumorigenesis and metastasis.


Subject(s)
Drosophila Proteins , Mitogen-Activated Protein Kinases , Oncogenes , Point Mutation , Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Cell Surface/genetics , 3T3 Cells , Animals , COS Cells , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cell Transformation, Neoplastic/genetics , HeLa Cells , Humans , JNK Mitogen-Activated Protein Kinases , Lung Neoplasms/pathology , Mice , Mice, Nude , Mitogen-Activated Protein Kinase 1 , Neoplasm Metastasis , Phenotype , Phosphorylation , Protein Kinases/metabolism , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-kit/genetics , Proto-Oncogene Proteins c-ret , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Cell Surface/metabolism , Sarcoma, Experimental/pathology , Signal Transduction
9.
Oncogene ; 12(12): 2697-703, 1996 Jun 20.
Article in English | MEDLINE | ID: mdl-8700529

ABSTRACT

CDC25Mm is a mouse guanine nucleotide exchange factor specific for Ras, exclusively expressed in the brain. We used a reporter gene containing a Ras-responsive fos-promoter in order to gain information on the role played by this exchange factor in signal transduction. Transient expression of CDC25Mm in CHO cells activates Ras. Moreover serum, but not insulin, can upregulate the response mediated by CDC25Mm and this modulation requires that the CDC25Mm maintains its N-terminal region. NIH3T3 fibroblasts, stably overexpressing this exchange factor, show a partially transformed phenotype, suggesting that the Ras-dependent pathway is constitutively active. In these cells serum and lysophosphatidic acid (LPA) stimulate Ras activity above the basal level while PDGF does not. Both serum and LPA-induced Ras activations in CDC25Mm overexpressing cells can be completely inhibited by pertussis toxin. Moreover, these responses are strongly reduced by coexpression of a truncated version of CDC25Mm lacking the C-terminal catalytic portion. This construct behaves in a dominant negative manner suggesting that it may compete with CDC25Mm by sequestering in an unproductive way signalling components activated by these factors. The data presented indicate that CDC25Mm does not participate in connecting tyrosine kinase receptors with Ras, while it could mediate Ras activation induced by pertussis toxin sensitive Gi-coupled receptors.


Subject(s)
Brain/metabolism , Cell Cycle Proteins/metabolism , Genes, ras , Phosphoprotein Phosphatases/metabolism , Signal Transduction , 3T3 Cells , Animals , Brain Chemistry , CHO Cells , Cell Cycle Proteins/drug effects , Cell Cycle Proteins/genetics , Cricetinae , Culture Media, Serum-Free/pharmacology , Gene Expression Regulation, Neoplastic , Insulin/pharmacology , Lysophospholipids/pharmacology , Mice , Phosphoprotein Phosphatases/drug effects , Phosphoprotein Phosphatases/genetics , Platelet-Derived Growth Factor/pharmacology , Receptor Protein-Tyrosine Kinases/metabolism , ras-GRF1
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