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Biomedical subjects

G Cantarella

Publications and source records attributed to G Cantarella.

At least 19 recordsLinked to original sources
PubMed2006

TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma cells.

Tumour growth is tightly related to new blood vessel formation, tissue remodelling and invasiveness capacity. A number of tissular factors fuel the growth of glioblastoma multiforme, the most aggressive brain neoplasm. In fact, gene array analyses demonstrated that the proapoptotic cytokine tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibited mRNA expression of VEGF, along with those of matrix metalloproteinase-2 (MMP-2), its inhibitor tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), as well as the tumour invasiveness-related gene secreted protein acid rich in cysteine (SPARC) in different human glioblastoma cell lines. Particularly, VEGF mRNA and protein expression and release from glioblastoma cells were also inhibited by TRAIL. The latter also exerted antimitogenic effects on human umbilical vein endothelial cells (HUVECs). With the same cells, TRAIL inhibited new vessel formation in the in vitro matrigel model, as well as it exerted powerful inhibition of blood vessel formation induced by an angiogenic cocktail administered in subcutaneous pellets in vivo in the C57 mouse. Moreover, the expression of MMP-2, its inhibitor TIMP-2 and the tumour invasiveness-related protein SPARC were effectively inhibited by TRAIL in glioblastoma cell lines. In conclusion, our data indicate that TRAIL inhibits the orchestra of factors contributing to glioblastoma biological aggressiveness. Thus, the TRAIL system could be regarded as a molecular target to exploit for innovative therapy of this type of tumour.

Animals↗
PubMed2004

Protective effects of estradiol on TRAIL-induced apoptosis in a human oligodendrocytic cell line: evidence for multiple sites of interactions.

Demyelinating diseases are high impact neurological disorders. Steroids are regarded as protective molecules in the susceptibility to these diseases. Here, we studied the interactions between tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent proapoptotic molecule toxic to oligodendrocytes, and 17-beta-estradiol (E-17-beta), in human oligodendrocytic MO3.13 cells. Exposure of cells to TRAIL resulted in the upregulation of both death receptors DR4 and DR5 and apoptosis, as well as the activation of caspase-8 and -3, increased phosphorylation of Jun-N-terminal kinase and p38 kinase, and the reduction of bcl-2 and bcl-xL proteins. TRAIL-mediated MO3.13 cell apoptosis was abrogated by the dominant-negative form of the adaptor protein FADD and by caspase inhibitors. Preincubation with E-17-beta completely prevented both TRAIL-induced DR4 and DR5 upregulation and apoptosis. Estrogen-induced cytoprotection was time and concentration dependent and reverted by antiestrogens. Estrogen treatment per se reduced kinase phosphorylation, and upregulated bcl-2 and bcl-xL proteins. In conclusion, our data show that the detrimental role of TRAIL on oligodendrocytes can be effectively counteracted by estrogens, thus suggesting that the underlying molecular interactions can be of potential relevance in characterizing novel targets for therapy of demyelinating disorders.

Apoptosis↗
PubMed2003

Neutralization of TRAIL death pathway protects human neuronal cell line from beta-amyloid toxicity.

Here we report that a novel member of the TNF-alpha family, TNF-related apoptosis-inducing ligand (TRAIL), contributes substantially to amyloid-induced neurotoxicity in human SH-SY5Y neuronal cell line. Involvement of TRAIL in the amyloid-induced cell death is supported by cDNA array, Northern blot, and Western blot data, demonstrating increased TRAIL expression after treatment of the cells with a neurotoxic fragment of amyloid protein (betaAP). TRAIL was also found to be released in the culture media after betaAP treatment with a time-course overlapping to contents of the intracellular protein. Contribution of TRAIL to betaAP neurotoxicity is demonstrated by data showing that TRAIL-neutralizing monoclonal antibody protects neuronal SH-SY5Y cells from betaAP neurotoxicity. Moreover, exposure of neuronal SH-SY5Y cells to TRAIL leads to cell death, indicating that this substance per se is endowed with neurotoxic properties. We also found that, similarly to betaAP and TRAIL, activation of the death-domain adaptor protein FADD results in neuronal cell death. Lack of FADD function, by overexpression of its dominant negative, rescued cells from either TRAIL- or betaAP-induced neurotoxicity, supporting the hypothesis that these three molecules share common intracellular pathways. Finally, we found that betaAP strongly activated caspase-8, and the cell-permeable, selective caspase-8 inhibitor z-IETD-FMK prevents both betaAP- and TRAIL-induced neurotoxicity. In view of TRAIL's potency in inducing neuronal death, and its role as mediator of betaAP, it is plausible to hypothesize that TRAIL can be regarded as a molecule that provides substantial contribution to betaAP-dependent cell death, which takes part in the progression of the neurodegenerative process and related chronic inflammatory response.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Tamoxifen inhibits nerve growth factor-induced proliferation of the human breast cancerous cell line MCF-7.

An array of polypeptide growth factors contribute to the development of breast cancer, the most common tumor-related cause of death in women of Western countries. Therefore, breast cancer therapy should be aimed at inhibition of growth factor-dependent breast cancerous cell proliferation. However, the relative contribution of each individual factor in the development and maintenance of the transformed phenotype is largely unknown. Here we report for the first time that the proliferative effects of nerve growth factor, (NGF) a typical neurotrophin, are similar to those of epidermal growth factor (EGF) and insulin-like growth factor II, and are enhanced by 17beta-estradiol in the human breast cancer cell line MCF-7. The effect of NGF appeared to be mediated by its trkA receptors (trkA(NGFR)), as suggested by the potent inhibition of both MCF-7 cell proliferation and trkA(NGFR) phosphorylation occurring upon treatment of cultures with the selective trkA(NGFR) inhibitor K252a. Surprisingly, the antiestrogen drug tamoxifen (TAM) inhibited NGF-induced MCF-7 cell proliferation and trkA(NGFR) phosphorylation in a concentration-related fashion. The effect of TAM seemed to be estrogen receptor-independent, because the pure estrogen receptor antagonist ICI 182.780 was unable to block NGF-induced trkA(NGFR) phosphorylation. Our data underline the new emerging role of trkA(NGFR) in breast tumor growth, and suggest a related novel therapeutic use of TAM in breast cancer.

Animals↗
PubMed2001

Increased ACTH and cortisol secretion after interleukin-alpha injection in the common marmoset (Callithrix jacchus jacchus).

We have studied the effect of intravenous injection of interleukin-1 (dose range: from 0.25 to 4.5 microg/kg of body weight) on plasma ACTH and cortisol levels in the marmoset, a primate paradygm of peripheral glucocorticoid resistance. Blood sampling were collected and body temperature recorded 0, 15, 30, 60, 120, 180, 240 and 300 min after injection. Interleukin-1 stimulated secretion of ACTH in a dose-dependent fashion. Maximal secretion occurred 120 min after injection, and lasted up to 240 min. Plasma ACTH levels returned to baseline 300 min after interleukin-1 injection. Plasma cortisol levels were related to ACTH levels. Body temperature elevation, which occurred 10-15 min after injection was dose-dependent, and lasted 3 h. Results suggest that the pyrogenic effect of interleukin is associated, in the marmoset, with integrated activation of the hypothalamic-pituitary-adrenal axis. In light of the proneness of marmosets to hyperimmune disorders, our data are consistent with the hypothesized central biological role of IL-1, as well as the pathophysiological relevance of the neuro-endocrine-immune cross-talk during the acute phase response.

Adrenocorticotropic Hormone↗
PubMed2001

Spindle cell lipoma of the hypopharynx.

Larynx and hypopharynx lipomas are reported to account for approximately 0.6% of benign laryngeal neoplasms. Spindle cell lipoma is a histologically distinct variant characterized by mature adipocytes mixed with collagen-forming spindle cells; only one case of spindle cell lipoma of the larynx has been previously reported. We here describe a new case of spindle cell lipoma of the pyriform sinus successfully treated by means of endoscopic surgical excision. A 77-year-old woman with a 40-year history of dysphagia reported that the condition had markedly worsened over the three years before she came to us. She had difficulty swallowing even semisolid food and she experienced occasional nasal regurgitation of liquid or solid food. Flexible videolaryngoscopy showed a very large mass, covered by normal mucosa that almost totally occupied the right pyriform sinus and was apparently attached to the right arytenoid. Functional endoscopic study and videofluoroscopy of swallowing showed that the bolus progressed exclusively in the left pyriform sinus, with postdeglutitory pooling in the right pyriform sinus and a reflux toward the valleculae during consecutive deglutitions. Computed tomography demonstrated that the hypopharyngeal mass had low attenuation values and negative densitometry. The entire mass was surgically removed during suspension microlaryngoscopy. The histological sections showed mature adipocytes mixed with small and slender spindle cells. Postoperative endoscopic and videofluorosocpic deglutition studies revealed the recovery of normal swallowing. This case indicates that hypopharyngeal lipomas should be included in the differential diagnosis of slowly occurring swallowing impairments.

Aged↗
PubMed2001

Divergent effects of corticotropin releasing hormone on endothelial cell nitric oxide synthase are associated with different expression of CRH type 1 and 2 receptors.

1. Endothelium is a target for an array of factors involved in inflammation. Endothelial cells express receptors for CRH, a neuropeptide produced during inflammation. We report both the concentration-dependent inhibitory effect of CRH upon cytokine-stimulated nitrite release by H5V murine endothelioma cells, and its stimulatory one in HUVEC cells. 2. Western blot analysis showed that CRH inhibits cytokine-stimulated iNOS protein in H5V cells, and, instead, potentiated it in HUVEC cells. 3. H5V cells expressed both CRH receptors (CRH-R1 and R2) mRNAs, whereas HUVEC cells expressed the CRH-R2 mRNA solely. 4. CRH increased medium nitrites and iNOS protein expression in H5V cells pretreated with the selective CRH-R1 antagonist CP 154,526. However, the selective CRH-R2 antagonist anti-Svg-30 failed to produce similar effects. In fact, anti-Svg-30 inhibited CRH-induced increase of nitrite release and iNOS expression in HUVEC cells. 5. Our results confirm the activating role of CRH on endothelial cells, although it suggests its possible inhibitory role in the late phase of the inflammatory response. NO-mediated effects of CRH on endothelial cells could be exploited in therapeutic strategies related to inflammatory and/or degenerative diseases.

Animals↗
PubMed2001

Bilateral laryngeal pseudoparalysis in xanthoma disseminatum treated by endoscopic laser medial arytenoidectomy.

Xanthoma disseminatum is a rare non-Langerhans' cell histiocytosis, characterized by papular cutaneous eruption, possible mucosal involvement, and frequent association with vasopressin-sensitive diabetes insipidus. Herein we report a case of xanthoma disseminatum with pharyngolaryngeal involvement. In this patient, mucosal xanthomas involving the arytenoid cartilages and the interarytenoid area resulted in laryngeal stenosis and severe impairment of both cricoarytenoid joints' motility. Endoscopic CO2 laser medial arytenoidectomy, according to the technique described by Crumley (1993), and vaporization of interarytenoid xanthomas were successfully performed, thus reestablishing bilateral cordal motility and the laryngeal airway. Four years later, a CO2 laser revision was necessary because of recurrence of xanthomas in the posterior larynx. Two years after the latter operation, the patient has no signs of laryngeal obstruction and has a normal voice quality. This case report suggests that endoscopic medial arytenoidectomy may be successfully used in the treatment of bilateral laryngeal pseudoparalysis secondary to xanthoma disseminatum.

Adult↗
PubMed2001

Increased frequency dependence of specific airway resistance in patients with laryngeal hemiplegia.

The aim of this study was to investigate whether patients with laryngeal hemiplegia (LH) show a frequency-dependent increase in specific airway resistance (sRaw), measured by body plethysmography. In addition to the flow-volume loop, usually considered in the functional evaluation of upper airway obstructions, variations in sRaw at respiratory frequencies of 30+/-5 (=0.5 Hz), 60+/-5 (=1 Hz) and 90+5 breaths x min(-1) (=1.5 Hz) in 21 never-smoking patients (LH group, mean age+/-SD 55+/-12.09 yrs; 17 females) whose unilateral vocal-cord paralysis was documented by laryngoscopy and who had no signs or symptoms of other respiratory diseases studied. They were compared to 21 healthy control subjects (C group: 50.1+/-15.44 yrs; 10 females). The sRaw values at 30+/-5 breaths min(-1) were similar in the two groups (5.54+/-1.88 versus 5.68+/-1.06 cmH2O x s(-1); p=NS), but at increasing frequencies (30+/-5, 60+/-5 and 90+/-5 breaths min(-1)), they progressively and significantly increased in the LH patients (from 5.54+/-1.88 to 6.63+/-1.96 and 8.05+/-2.6 mH2O x s(-1); p<0.0005), and not significantly in controls (5.68+/-1.06, 5.85+/-0.95 and 5.9+/-1.12 cmH2O x s(-1); p=NS). Linear discriminant analysis using AsRaw (sRaw at 1.5 Hz-sRaw at 0.5 Hz) and forced inspiratory flow at 50% of the vital capacity made it possible to correctly classify all of the controls and 19 of the 21 patients. In conclusion, the multiple, rapid and noninvasive plethysmographical testing of frequency-dependent increase in specific airway resistance with the flow-volume loop, allows the sufficiently satisfactory discrimination of laryngeal hemiplegia patients from controls.

Adult↗
PubMed2000

Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation.

The adapter protein RIP plays a crucial role in NF-kappaB activation by TNF. Here we show that triggering of the p55 TNF receptor induces binding of RIP to NEMO (IKKgamma), a component of the I-kappa-B-kinase (IKK) "signalosome" complex, as well as recruitment of RIP to the receptor together with the three major signalosome components, NEMO, IKK1 and IKK2, and some kind of covalent modification of the recruited RIP molecules. It also induces binding of NEMO to the signaling inhibitor A20, and recruitment of A20 to the receptor. Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex.

Antigens, CD↗
PubMed2000

Responsiveness of irradiated rat anterior pituitary cells to hypothalamic releasing hormones is restored by treatment with growth hormone.

Hypopituitarism is a common sequela of irradiation in cancer patients. Here we report that recombinant human growth hormone (r-hGH) prevents cell death and restores secretory capacity of irradiated rat pituitary cells in vitro. Dispersed rat pituitary cells from male Sprague-Dawley rats, irradiated with a 9-Gy sublethal dose, were incubated with r-hGH before, after, or before and after irradiation. Treatment with GH resulted in increased cell survival, which reached its maximum at the concentration of 5 nM, with an EC(50) of 3.5 nM. Protective effects of GH on pituitary cells were more pronounced in cultures treated before and after irradiation. Similarly, beneficial effects of GH were observed on the secretory capacity of surviving cells. In fact, irradiated pituitary cells treated with GH secreted substantial amounts of GH, luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone and adrenocorticotropic hormone in response to specific releasing hormones. Such effects of GH were prevented in the presence of the specific GH receptor antagonists B2036 and G120K. Our results show that r-hGH exerts a specific protective effect on irradiated rat pituitary cells and suggest possible use of GH as an adjuvant agent for prevention of postirradiation hypopituitarism.

Adrenocorticotropic Hormone↗
PubMed1999

Thymic hormones, cancer and behavioural adaptive responses.

The effects of thymic hormones are not restricted within the immune system but are rather pleiotropic. Through neuropeptides the neuroendocrine system participates in the regulation of homeostasis as well as in the control of stress response and behavioural outputs. Thymic hormones increase spontaneous behaviour, inhibit anxiety-like responses and improve resistance to stress in tumour-bearing mice. In addition, thymic hormones modulate secretion of pituitary adrenocorticotrophin (ACTH) and beta-endorphin in both primates and rodents. In turn, both ACTH and beta-endorphin influence stress response and behaviour. Besides their neuroendocrine effects, thymic hormones have radioprotective effects either when administered alone or when associated with other radioprotective agents. Thymic hormones are possibly able to reduce postirradiation tissue damage in the bone marrow and in the central nervous system. Finally, evidence suggests a potentiating effect of thymic hormones when associated with current anticancer drugs. From the data reviewed it seems reasonable to conclude that the combination of thymic hormones with cancer therapy is associated with improvement of behaviour and well-being status, protection of tissues from detrimental effects of cancer treatment, and possibly also with potentiation of the antiproliferative effects of other drugs. Thus, thymic hormones could be envisioned as a valuable adjunct to actual cancer therapy.

Adjuvants, Immunologic↗
PubMed1998

A possible sequela of transoral approach to the upper cervical spine. Velopharyngeal incompetence.

The authors describe a case of velopharyngeal incompetence (VPI), as a consequence to the neurosurgical treatment for a complex malformation of the cranio-spinal junction. A 61-year-old woman underwent a transoral-transvelar surgical approach for odontoid resection. One month later surgical fixation of the posterior spine with autologous iliac bone graft was performed. Following these operations the patient presented a marked alteration of speech intellegibility due to hypernasal voice resonance and through incapability to articulate the oral phonemes correctly. She also complained of nasal regurgitation of fluids and solids while swallowing. She underwent a clinical phoniatric assessment of voice and speech. Videonasopharyngoscopy allowed us to inspect the velopharyngeal sphincter and to show clearly the type and morphology of its closure defect. Correction of VPI was achieved by means of a velopharyngoplasty (pharyngeal flap), in spite of technical difficulties due to local scarring and to a problematic exposure of the surgical field.

Cervical Vertebrae↗
PubMed1997

Guidelines for the therapeutic use of botulinum toxin in movement disorders. Italian Study Group for Movement Disorders, Italian Society of Neurology.

Since its introduction in the early '80s the use of botulinum toxin has improved the quality of life of the patients affected by movement disorders. Toxin's neuromuscular blocking action allows a symptomatic treatment of those clinical conditions characterised by excessive muscular activity. Although the dosages used are safe and the side-effects are reversible, a correct use of botulinum toxin depends on the knowledge of its clinical pharmacology and of the anatomy of the body segments to be injected. In addition, the treatment of more complex conditions, i.e. laringeal dystonia, imposes an inter-disciplinary approach and specialised injection techniques. In this review, the Italian Study Group on Movement Disorders presents the consensus guidelines for the therapeutic use of botulinum toxin in movement disorders. The main toxin types, their use and administration modalities, and the training guidelines will be presented.

Botulinum Toxins↗
PubMed1995

The phospholipid drug glyceryl-phosphoryl-O-serine modulates pituitary adrenocorticotropin and hypothalamic corticotropin releasing hormone in vitro secretion in the aging rat.

We have investigated the effects of the novel phospholipid drug glyceryl-phosphoryl-O-serine (GPS) on pituitary ACTH and hypothalamic corticotropin releasing hormone secretion in vitro in cultures from both 2- and 24 month-old Sprague-Dawley rats. Basal levels of ACTH in primary cultures of pituitary cells from 24 month-old rats were lower than (100 +/- 12 pg/10(5) cells) in 2 month-old rats (207 +/- 18 pg/10(5) cells). Basal medium corticotropin releasing hormone levels in hypothalamic cultures were higher in 24 month-old rats (45 +/- 7 pg/well/20 min.), than in 2 month-old rats (29 +/- 5.5 pg/well/20 min). Treatment of both pituitary cells with corticotropin releasing hormone and hypothalami with serotonin resulted respectively in a significant, concentration-dependent, increase of medium ACTH and corticotropin releasing hormone. However, concentration-response curves for ACTH and corticotropin releasing hormone were shifted to the right in cultures from 24 month-old rats. Incubation with graded concentrations of GPS produced significant increase in medium ACTH and corticotropin releasing hormone in cultures from 24 month-old rats, whereas the drug was ineffective in stimulating secretion of both hormones from 2 month-old rat cells. In addition, the adenylate cyclase stimulator forskolin and the protein kinase C activator oleyl-acyl-glycerol stimulated ACTH secretion in pituicytes from rats of both ages. However, response to oleyl-acyl-glycerol was blunted in pituicytes from 24 month-old rats. Combination of either forskolin or oleyl-acyl-glycerol with GPS resulted in a potentiation of the effect. Our data confirm an impairment of both pituitary ACTH and hypothalamic corticotropin releasing hormone secretion in the aging rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Compatibility of reduced glutathione (GSH) with different solutions currently used in anesthesia and reanimation.

BACKGROUND: Reduced glutathione (GSH) an antioxidant used for i.v. or i.m. administrations, prepared as powder to be diluted in distilled water just before injection (Tationil 600), could lose its antioxidant properties when added to various infusions currently utilized in anesthesia and reanimation. AIM OF THE WORK: Evaluate in vitro the compatibility of the compound marketed under the trade nome "Tationil 600" with the intravenous infusions in common use in anesthesia and reanimation. MATERIALS AND METHODS: 10 mg GSH (Tationil 600) were added to 10 ml of different solutions: 0.9% saline (I), 5% glucosate solution (II), Normosol-M and 5% glucose (III), 3.5% Emagel (IV), Propofol 10 mg/ml (V), in order to obtain a final solution containing 1 mg og GSH per ml of solution. The different solutions were incubated and aliquots taken at different times and analyzed. RESULTS: GSH in its commercial preparation proved to be compatible with all solutions examined with exception of solution III, because of the interference of sodium bisolfite. CONCLUSIONS: Reduced glutathione (Tationil 600) was compatible with solutions I, II, IV and V, used for i.v. administrations in anesthesia and reanimation, and revealed to maintain its antioxidant properties when studied over a period of 24 hours.

Anesthesia↗
PubMed1994

Effects of pidotimod on the immune and the neuroendocrine system in the aging rat.

The effects of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a synthetic thymic dipeptide, on immune response in 2 and 24 month-old rats were investigated. Peripheral blood lymphocytes and splenocytes of aging rats treated for 1 week with different doses of pidotimod showed increased rates of mitogen-stimulated proliferation. Also, interleukin-2 production by 24 month-old rat lymphocytes was significantly increased after treatment with the drug. In addition, the response of the hypothalamic-pituitary-adrenal (HPA) axis to interleukin-1 in 2 and 24 month-old Sprague-Dawley rats previously treated with pidotimod was studies. Blood samples were withdrawn--30, 0, 30, 60, 90 and 120 min after interleukin-1 injection. Interleukin-1 injection stimulated ACTH secretion in a dose-related manner, in both 2 and 24 month-old rats. Peak of the effect was 60 min after the injection. ACTH levels returned to baseline within 120 min in 2 month-old rats, whereas they were still high in untreated 24 month-old rats. However, plasma ACTH levels at 120 min were significantly lower in 24 month-old rats treated with pidotimod. Results suggest that pidotimod possesses immunomodulating properties, such as enhancement of splenocyte and peripheral blood lymphocyte proliferation, and improvement of the deficitary feedback mechanism between the hypothalamic-pituitary-adrenal axis and cytokines and, namely, interleukin-1 in the aging rat.

Adjuvants, Immunologic↗