[Show abstract][Hide abstract] ABSTRACT: Uveal melanoma (UM) represents approximately 5-6% of all melanoma diagnoses and up to 50% of patients succumb to their disease. Although several methods are available, accurate diagnosis is not always easily feasible because of potential accidents (e.g., intraocular hemorrhage). Based on the assumption that the profile of circulating miRNAs is often altered in human cancers, we verified whether UM patients showed different vitreous humor (VH) or serum miRNA profiles with respect to healthy controls. By using TaqMan Low Density Arrays, we analysed 754 miRNAs from VH, vitreal exosomes, and serum of 6 UM patients and 6 healthy donors: our data demonstrated that the UM VH profile was unique and only partially overlapping with that from serum of the same patients. Whereas, 90% of miRNAs were shared between VH and vitreal exosomes, and their alterations in UM were statistically overlapped with those of VH and vitreal exosomes, suggesting that VH alterations could result from exosomal dysregulation. We report 32 miRNAs differentially expressed in UM patients in at least two different types of samples analyzed. We validated these data on an independent cohort of twelve UM patients. Most alterations were common to VH and vitreal exosomes (e.g., upregulation of miR-21,-34a,-146a). Interestingly, miR-146a was upregulated in the serum of UM patients, as well as in serum exosomes. Upregulation of miR-21 and miR-146a was also detected in formalin-fixed, paraffin-embedded UM, suggesting that VH or serum alterations in UM could be the consequence of disregulation arising from tumoral cells. Our findings suggest the possibility to detect in VH and serum of UM patients "diagnostic" miRNAs released by the affected eye: based on this, miR-146a could be considered a potential circulating marker of UM.
Cancer biology & therapy 05/2015; DOI:10.1080/15384047.2015.1046021 · 3.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose This study was undertaken to compare the ultrasound and magnetic resonance imaging parameters of ocular melanoma and to assess their variation after proton-beam therapy. Materials and methods Fifteen choroidal melanoma patients treated with proton-beam therapy were enroled in the study. All patients underwent ophthalmologic evaluations, ultrasound, conventional magnetic resonance (MR) imaging and diffusion-weighted MR imaging before the start of therapy and 3 and 6 months after therapy. Basal diameters, thickness, internal reflectivity, tumour volumes and apparent diffusion coefficient (ADC) values of ocular melanomas were measured at each examination. Correlations between internal reflectivity and ADC were investigated. Results No significant changes were seen in tumour diameters and tumour height as assessed by B-scan and A-scan, respectively. Significant increase in mean tumour internal reflectivity was detected at 6 months (baseline 35 % ± 11; 6 months 48 % ± 8, Tukey–Kramer p = 0.005). On MRI, compared to baseline (mean 547 ± 262 mm3), a significant reduction in volume was seen at 6 months (Tukey–Kramer p = 0.045) (mean volume 339 ± 170 mm3, mean reduction 38 %). A significant increase in ADC (baseline 1,002 ± 109 mm2/s) was detected both at 3 and 6 months after proton therapy (respectively, 1,454 ± 90 and 1,833 ± 261 mm2/s, both p Conclusions By MRI, in particular by ADC assessment, it is possible to detect early variations in melanoma treated by proton-beam therapy. This examination could be used together with ultrasound in the follow-up of this treatment.
La radiologia medica 02/2015; DOI:10.1007/s11547-015-0509-1 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the utility of diffusion-weighted magnetic resonance (MR) imaging for prediction and early detection of response to proton beam therapy in ocular melanoma.
Ten ocular melanoma patients treated with proton beam therapy were enrolled in the study. All patients underwent conventional MR imaging and diffusion-weighted imaging (DWI) before the start of therapy, and after 1, 3 and 6 months of therapy. Tumour volumes and apparent diffusion coefficient (ADC) values of ocular lesions were measured at each examination. Tumour volumes and mean ADC measurements of the four examination series were compared; correlation of ADC values and tumour regression was investigated.
Mean ADC value of ocular melanomas significantly increased as early as 3 months after therapy; tumour volume significantly decreased as early as 6 months after therapy. The ADC values of ocular melanomas before therapy significantly correlated with tumour regression.
DWI may provide an early surrogate biomarker for prediction and early detection of tumour response to eye-preserving therapies in ocular melanoma.
La radiologia medica 01/2015; 120(6). DOI:10.1007/s11547-014-0488-7 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Melanoma arising from melanocytes within the choroid is the most frequent primary intraocular neoplasm in adults. It is biologically distinct from cutaneous melanoma by a very strong propensity to metastasize the liver. Raf kinase inhibitor protein is a member of an evolutionarily conserved group of proteins called phosphatidylethanolamine-binding proteins. It is an interacting partner of Raf-1 and a negative regulator of the mitogen-activated protein kinase cascade initiated by Raf-1. Raf kinase inhibitor protein expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. In the present study, we examined the immunohistochemical expression levels of Raf kinase inhibitor protein and phosphorylated Raf kinase inhibitor protein in primary uveal melanoma with and without metastasis, and evaluated their association with other high risk characteristics for metastasis in order to assess whether Raf kinase inhibitor protein and phosphorylated Raf kinase inhibitor protein can be used to predict metastasis. A significant low expression of Raf kinase inhibitor protein was seen in patients with metastasis but not in patients without metastasis. The latter more frequently had a high expression of Raf kinase inhibitor protein. No significant difference was seen in phosphorylated Raf kinase inhibitor protein expression between patients with and without metastasis. Raf kinase inhibitor protein expression is a suitable and easily determinable marker in the primary tumour that could predict the risk of uveal melanoma to metastasize, and hence guide strategies for monitoring and therapy.
Histology and histopathology 04/2014; · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acetaminophen intoxication is a leading cause of acute liver failure. Liver transplantation for acute liver failure is limited by the availability of donor organs. In this study, we aimed at identifying if the transplantation of adipose tissue-mesenchymal stem cells (ASCs) may exert therapeutic effects on acetaminophen-induced liver injury.
ASCs were isolated from human subcutaneous tissue and were transfected with a green fluorescent protein (GFP). Sprague-Dawley rats were administrated 300mg/kg of acetaminophen intraperitoneally and were transplanted with ASCs or vehicle. After 24h from acetaminophen administration, rats were sacrificed. Hepatic levels of isoprostanes, 8-hydroxyguanosine (8-OHG), nitrites/nitrates and reduced glutathione (GSH) were determined as markers of oxidative stress; JNK phosphorylation and hepatic levels of inflammatory cytokines and regeneration factors were also assessed.
Transplantation of ASCs decreased AST, ALT and prothrombin time to the levels observed in control rats. Transplanted animals had normal plasma ammonia and did not display clinical encephalopathy. Liver sections of intoxicated rats treated with vehicle showed lobular necrosis and diffuse vacuolar degeneration; in rats transplanted with ASCs liver injury was almost absent. Transplantation of ASCs decreased liver isoprostanes, 8-OHG and nitrite-nitrates to the levels of control rats, while preserving GSH. Consistently, hepatic levels of TNF-α, MCP-1, IL-1β, ICAM-1 and phospho-JNK were markedly increased in rats treated with vehicle and were restored to the levels of controls in animals transplanted with ASCs. Furthermore, ASC transplantation increased liver expression of cyclin D1 and PCNA, two established hepatocyte regeneration factors, whereas ASCs were not able to metabolize acetaminophen in vitro.
In this study, we demonstrated that ASC transplantation is effective in treating acetaminophen liver injury by enhancing hepatocyte regeneration and inhibiting liver stress and inflammatory signaling.
Stem Cell Research 07/2013; 11(3):1037-1044. DOI:10.1016/j.scr.2013.07.003 · 3.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Developmental expression of Wilms' tumor gene (WT1) and protein is crucial for cell proliferation, apoptosis, differentiation and cytoskeletal architecture regulation. Recently, a potential role of WT1 has been suggested in the development of neural tissue and in neurodegenerative disorders. We have investigated immunohistochemically the developmentally regulated expression and distribution of WT1 in the human fetal peripheral sympathetic nervous system (PSNS) and the gastro-enteric nervous system (GENS) from weeks 8 to 28 gestational age. WT1 expression was restricted to the cytoplasm of sympathetic neuroblasts, while it progressively disappeared with advancing morphologic differentiation of these cells along both ganglionic and chromaffin cell lineages. In adult tissues, both ganglion and chromaffin cells lacked any WT1 expression. These findings show that WT1 is a reliable marker of human sympathetic neuroblasts, which can be used routinely in formalin-fixed, paraffin-embedded tissues. The progressive loss of WT1 in both ganglion and chromaffin cells, suggests its potential repressor role of differentiation in a precise temporal window during the development of the human PSNS and GENS.
[Show abstract][Hide abstract] ABSTRACT: Background/Aims: We evaluated the diagnostic variability and reproducibility of endoscopic signs in two populations with a different pretest likelihood of celiac disease (CD). Methods: We recruited 289 CD patients (both adults and children) in a multicenter prospective study. Group 1 (high risk) included 111 patients referred for positive serology. Group 2 (low risk) included 178 unselected patients. Mosaic pattern, reduction/loss of Kerckring's folds, scalloping of the valvulae conniventes and a nodular pattern were the endoscopic findings looked for in the duodenum. Results: In group 1, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of endoscopic findings were 100, 84.6, 94.2 and 100% in adults, and 86.8, 9.1, 82.1 and 12.5% in children. In group 2, the sensitivity, specificity, PPV and NPV of endoscopic findings were 33.3, 91.4, 7.7 and 98.5% in adults, and noncalculable, 78.3, 0.0 and 100% in children. Comparing group 1 and group 2, there was a statistically significant difference in sensitivity and PPV in adults, and in specificity, PPV and NPV in children. Concerning the reproducibility of endoscopic findings, a wide variability of κ values was found. Conclusion: Endoscopic signs have low reproducibility for CD, and their diagnostic value in selecting patients for multiple intestinal biopsies is unacceptable, especially in populations with low disease prevalence.
[Show abstract][Hide abstract] ABSTRACT: Based on evidence that microRNAs (miRNAs) are found in many biologic fluids (e.g., urine, saliva, pleural fluid), we sought to detect the presence of miRNAs and analyze their profile in vitreous humor (VH) from patients affected by various ocular diseases.
MiRNAs were purified from VH samples taken during vitrectomy, by using the Qiagen miRNeasy Mini Kit. The expression profile on 745 miRNAs was performed by using TaqMan Low Density Array. Single TaqMan expression assays were performed on 18 VH samples (six each from patients with choroidal melanomas, retinal detachment, or macular hole) for miRNAs commonly expressed in serum or retinal cells: let-7b, miR-21, miR-26a, miR-146a, miR-199-3p, miR-210, miR-374a*, miR-532-5p. RNA extracted from serum of six healthy donors or from formalin-fixed, paraffin-embedded samples of choroidal melanocytes from four uveal melanomas (epithelioid cells) and from three unaffected eyes were used as controls.
We identified the presence of 94 circulating small RNAs in the vitreous, some of which (miR-9, miR-9*, miR-125a-3p, miR-184, miR-211, miR-214, miR-302c, miR-452, miR-628, miR-639) are particularly abundant in the VH but downrepresented or not detectable in serum. MiR-146a and miR-26a were overexpressed more than threefold in VH from patients with uveal melanomas compared to the other pathological groups (Wilcoxon signed-rank test, p value <0.05).
Our experimental data suggest that a specific set of circulating miRNAs is secreted in the vitreous, which is quite different from the miRNA pattern in serum, and that the quantity of vitreal miRNAs could change, depending on the pathologies of the eye.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The main cause of treatment failure and death in laryngeal squamous cell carcinoma is metastasis to the regional lymph nodes. The current clinical staging criteria fail to differentiate patients with occult metastasis from patients without metastasis. Identifying molecular markers of the disease might improve our understanding of the molecular mechanisms underlying the pathogenesis and development of laryngeal carcinoma and may help improve clinical staging and treatment. METHODS: Sixty-four previously untreated patients who underwent surgical excision of laryngeal squamous cell carcinoma with neck dissection were included in this study. The expression of B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) was examined immunohistochemically on formalin-fixed paraffin-embedded primary tissue specimens. RESULTS: Nuclear expression of BMI-1 (nBMI-1) was detected in 32 of the 64 tumors (50%), cytoplasmic expression of BMI-1 (cBMI-1) was detected in 22 (34.4%), and 10 tumors (15.6%) showed no BMI-1 immunoreactivity. High nBMI-1 expression levels (>=10) were detected in 28 of the 32 (87.5%) nBMI-1-positive patients. Multivariate analysis including age at diagnosis, grade, tumor location, TNM status, and nBMI-1 expression showed that a high nBMI-1 expression level was an independent prognostic factor for lymph node metastasis. CONCLUSION: The expression of BMI-1 in patients with laryngeal carcinoma seems to correlate with lymph node metastasis.
World Journal of Surgical Oncology 10/2012; 10(1):206. DOI:10.1186/1477-7819-10-206 · 1.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity.
Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed.
Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity.
Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.
World Journal of Gastroenterology 08/2012; 18(29):3862-8. DOI:10.3748/wjg.v18.i29.3862 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphoma is the most common malignant orbital tumor. We describe the imaging features of diffuse orbital follicular lymphoma with extension into the pterygopalatine fossa and infratemporal fossa without bony infiltration.
[Show abstract][Hide abstract] ABSTRACT: Primary intestinal lymphoma is rare representing about 0.5% of all colonic malignancies. It can be classified into two principal categories: follicular B cell lymphomas and intestinal T cell lymphomas. Other intestinal diseases are very important such as immunoproliferative small intestinal disease (IPSID), a prelymphomatous process, and MALT lymphomas, caused by infection of Helicobacter pylori (H. Pylori). We present a 79-year-old male patient which presented with abdominal pain in the upper parts of abdomen of four months' duration, colic timpanists, tenderness, distention, weight loss. Sometimes the abdominal pain decreased expelling diarrheal dejections. Histological and immune-histochemical tests on bioptic piece helped to reach the diagnosis of lymphoma but only after histological investigation on operative piece was made the diagnosis of B-cell lymphoma. This case report shows that an accurate diagnosis, the evaluation of the extension and the presence of particular infections and/or co morbidities (H. Pylori positive, age, performance status) are fundamental to decide the therapeutic protocol.
European review for medical and pharmacological sciences 11/2011; 15(11):1347-51. · 0.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe the case of a 67-year-old woman affected by pemphigus vulgaris with a dry whitish scaly lesion in the upper lip. Clinically, this lesion resembled an actinic keratosis. Although histological examination revealed a focal acantholysis, the finding of a moderate-to-severe dysplastic epithelium was consistent with the diagnosis of acantholytic actinic keratosis with moderate/severe dysplasia. Nevertheless, the complete resolution of the lip lesion after systemic therapy for pemphigus vulgaris led us to reconsider the possibility that we were dealing with a pemphigus vulgaris with unusual clinical and histological features. The previously reported cytological dysplasia was better regarded reactive rather than neoplastic, likely as the result to the inflammatory injury.
Case Reports in Medicine 03/2011; 2011:518758. DOI:10.1155/2011/518758
[Show abstract][Hide abstract] ABSTRACT: Dual kidney transplantation (DKT) of marginal kidneys could offer transplant candidates a very satisfactory kidney transplantation in terms of renal function. However, DKT might be considered a major surgical procedure and, in older recipients, has a potentially greater risk of surgical complications compared with single kidney transplantation. Because of these findings, some transplant centers have replaced the classic bilateral placement of 2 kidneys with the monolateral placement of both kidneys.
In a group of 35 DKTs performed during a 5-year period, we applied a new technique of monolateral placement of DKT in 10 recipients. In these 10 patients, the arteries and veins of the 2 kidneys were joined through a running suture, and the joined kidneys were anastomosed into the external iliac vessels in the recipient.
The delayed graft function rate was 20%. No surgical complications developed in the entire series. One patient experienced late rejection with ureteral stricture. The graft and patient survival rate at a median follow-up of 30 months was 90%.
To reduce the surgical risk and morbidity rate, the monolateral placement of both kidneys seems the safest method to perform DKT. The joined monolateral DKT, by reducing the cold ischemia time and the surgical trauma, could represent a step forward in the delicate treatment of these patients.