Acute rapamycin rescues the hyperexcitable phenotype of accumbal medium spiny neurons in the valproic acid rat model of autism spectrum disorder.

We previously demonstrated that prenatal exposure to valproic acid (VPA), an environmental model of autism spectrum disorder (ASD), leads to a hyperexcitable phenotype associated with downregulation of inward-rectifying potassium currents in nucleus accumbens (NAc) medium spiny neurons (MSNs) of adolescent rats. Aberrant mTOR pathway function has been associated with autistic-like phenotypes in multiple animal models, including gestational exposure to VPA. The purpose of this work was to probe the involvement of the mTOR pathway in VPA-induced alterations of striatal excitability. Adolescent male Wistar rats prenatally exposed to VPA were treated acutely with the mTOR inhibitor rapamycin and used for behavioral tests, ex vivo brain slice electrophysiology, single-neuron morphometric analysis, synaptic protein quantification and gene expression analysis in the NAc. We report that postnatal rapamycin ameliorates the social deficit and reverts the abnormal excitability, but not the inward-rectifying potassium current defect, of accumbal MSNs. Synaptic transmission and neuronal morphology were largely unaffected by prenatal VPA exposure or postnatal rapamycin treatment. Transcriptome analysis revealed extensive deregulation of genes implied in neurodevelopmental disorders and ionic mechanisms exerted by prenatal VPA, which was partially reverted by postnatal rapamycin. The results of this work support the existence of antagonistic interaction between mTOR and VPA-induced pathways on social behavior, neurophysiological phenotype and gene expression profile, thus prompting further investigation of the mTOR pathway in the quest for specific therapeutic targets in ASD.

Moderate ethanol drinking is sufficient to alter Ventral Tegmental Area dopamine neurons activity via functional and structural remodeling of GABAergic transmission.

Earlier studies have shown a major involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons in mediating the rewarding effects of ethanol (EtOH). Much less is known on the role of this system in mediating the transition from moderate to excessive drinking and abuse. Here we sought to explore the hypothesis that early stage drinking in rodents, resembling recreational EtOH use in humans, is sufficient to dysregulate VTA DA transmission thus increasing the propensity to use over time. To this purpose, midbrain slice recordings in mice previously exposed to an escalating (3, 6 and 12%) 18-day voluntary EtOH drinking paradigm was used. By recording from DA and γ-aminobutyric acid (GABA) VTA neurons in midbrain slices, we found that moderate EtOH drinking leads to a significant suppression of the spontaneous activity of VTA DA neurons, while increasing their response to acute EtOH application. We also found that chronic EtOH leads to the enhancement of GABA input frequency onto a subset of DA neurons. Structurally, chronic EtOH induced a significant increase in the number of GABA axonal boutons contacting DA neurons, suggesting deep rewiring of the GABA network. This scenario is consistent with a downmodulation of the reward DA system induced by moderate EtOH drinking, a neurochemical state defined as "hypodopaminergic" and previously associated with advanced stages of drug use in humans. In this context, increased sensitivity of DA neurons towards acute EtOH may represent the neurophysiological correlate of increased unitary rewarding value, possibly driving progression to addiction.

Chymase-positive Mast cells correlate with tumor angiogenesis: first report in pancreatic cancer patients.

OBJECTIVE: Mast cells (MCs) are known to be involved in several physiological and pathological processes in humans and animals. Recently, their potential role in tumor development and angiogenesis has been investigated, arising interesting results to be potentially applied in clinics. Mast cells' granules contain a huge quantity of protease enzymes that, through different mechanisms, induce the formation of new microvessels, feeding tumor burden. Among them, tryptase and chymase are the most abundant enzymes: tryptase is well known for its multiple activities, on the contrary, the role of chymase in pancreatic cancer angiogenesis has not been investigated yet. PATIENTS AND METHODS: Our research aims to correlate to each other and to angiogenesis four different tissue parameters (MCs density positive to chymase, MCs area positive to chymase, microvascular density and endothelial area) together with the main clinical-pathological characteristics in 52 patients surgically resected for pancreatic ductal adenocarcinoma, employing immunohistochemistry and image analysis system. RESULTS: All reported tissue parameters match to confirm the correlation between chymase enzyme and angiogenesis in pancreatic cancer. CONCLUSIONS: This evidence could become a starting point for a new potential therapeutic route exploiting chymase inhibitors as a novel anti-angiogenetic strategy in pancreatic cancer patients.

Postoperative treatment with phytotheraphy Graminex G63 (CERNILEN-Flogo®) after greenlight laser XPS (180W) photovaporization of the prostate (PVP), can affect patient's quality of life?

OBJECTIVE: Phytotherapic treatment as Cernilen-flogo® is commonly used to treat chronic pelvic pain, chronic prostatitis, and BPE (benign prostatic enlargement). In our study, for the first time, we aim to evaluate postoperatively Cernilen-flogo® therapy in patients with BPE/LUTS (lower urinary tract symptoms) previously treated with Greenlight laser XPS (180W) photovaporization of prostate (PVP) to improve surgical outcomes. MATERIALS AND METHODS: We collected data from patients treated with PVP for BPE/LUTS international prostate symptom score (IPSS) >20 unresponding to conventional treatment. Two groups of patients were analyzed: Group A including 15 patients (50%) treated postoperatively with Cernilen-flogo® vs. no treatment Group B. One expert surgeon performed all the procedures. RESULTS: 30 patients included with BPE/LUTs previously treated with PVP. There was no difference between patients' demographic, median age, prostate volume and PSA (prostate specific antigen) level. All patients had a postoperative evaluation after 30-45 days. Patients with postoperative complications (acute urinary retention, postoperative hematuria) were excluded from our study. All patients had a preoperative and postoperative evaluation of IPSS, bother score (BS) and pelvic discomfort (visual analogic scale VAS). Preoperatively there was no significative difference in IPSS, BS and VAS. IPSS Group A was postoperatively 7.13 (SD 1.64) and Group B was 7.33 (SD 1.58) (p=0.67); BS Group A was postoperatively 1.33 (SD 0.81), Group B was 1.73 (SD 1.09) (p=0.30), and VAS Group A was 2.73 (SD 1.9) and Group B was 4.33 (SD 1.58) (p=0.004) showing a statistically significative difference between the two groups in pelvic discomfort with a better outcome in patients treated with Cernilen-flogo®. CONCLUSIONS: Our study showed that Cernilen-flogo® treatment after PVP is effective and minimize patient's pelvic discomfort showed by lower VAS level resulting in better postoperatively patient's quality of life (QOL).

Local treatment with deep percutaneous electrochemotherapy of different tumor lesions: pain relief and objective response results from an observational study.

OBJECTIVE: The aim of this investigation focuses on the evaluation of the efficacy of deep-seated Electrochemotherapy (ECT) in terms of pain relief and local objective response, in pre-treated patients with neither further available pharmacological treatments nor eligible for surgery. PATIENTS AND METHODS: Deep percutaneous ECT has been performed in 20 patients subjected to systemic anaesthesia. Bleomycin was administrated intravenously before the application of the electrical pulses on the target area, employing multiple single needles depending on the size and location of the target tumor. RESULTS: Pain assessment based on Visual Analogue Scale showed significant pain relief one month after treatment in all patients, reducing from 7.5 to 3 as a median value (p-value at Wilcoxon test <0.001). Local symptom-free survival median value was 5.5 months. At the first follow-up (1-2 months), a local disease control rate (LDCR) was observed in 19/20 (95%) patients: complete responses in 2 (10%), partial responses in 8 (40%) and stable disease in 9 (45%). Local progression-free survival median value was 5.7 months. Overall, no major adverse effects were observed. CONCLUSIONS: Our study indicates that deep percutaneous ECT can produce a significant pain reduction and a high LDCR in different tumor lesions, for anatomical site or histotype. In particular, ECT has demonstrated to be effective in various histotypes and deep-seated tumor lesions never treated before by this approach giving a new chance to physicians for reducing oncological pain in patients not eligible to other therapeutic routes. The innovative peculiarity of our study was the successful application of deep percutaneous ECT on adrenal metastasis, malignant pleural mesothelioma, uterine leiomyosarcoma and the uncommon case of a male müllerian tumor.

Analysis of Aortic Remodeling and Stiffness in Patients with Obstructive Sleep Apnea Syndrome: Preliminary Results.

Obstructive sleep apnea (OSA) is a well-known risk factor for cardiovascular diseases. Several studies have shown that OSA is associated with vessel remodeling, but few studies have examined aorta. AIM: to analyse aortic remodelling in OSA. METHODS: Thirty consecutive OSA patients (22 males and 8 females, aged 58.5 ± 13.2 years) were studied. All patients underwent a morning blood gas analysis, a full cardiorespiratory evaluation, including nocturnal polygraphy and echocardiography, that assessed aortic root diameter (ARD) and aortic stiffness index (ASI). Patients were grouped as follows: Group 1, non-severe OSA (Apnea-Hypopnea Index; AHI <30, 14 patients); Group 2, severe OSA (AHI ≥30, 16 patients). RESULTS: No difference was found between the groups in ARD as absolute value (Group 1, 33.64 ± 0.91 mm; Group 2, 33.64 ± 1.02, p = ns) and as normalized value for the body surface area - ARDi (Group 1, 16.72 ± 0.63 mm/m2; Group 2, 16.09 ± 0.44, p = ns). Moreover, no difference was found in the ASI (Group 1, 14.04 ± 2.26; Group 2, 13.41 ± 2.22, p = ns). Considering all OSA patients, AHI showed an inverse correlation with ARDi (p = 0.018) and ASI (p = 0.0449). Moreover, the ASI showed a direct correlation with ARDi (p = 0.01) and morning PaO2 (p = 0.0349) as well as an inverse correlation with the oxygen desaturation index (ODI, p = 0.031) and total time with apnea and hypopnea (p = 0.039). CONCLUSION: No difference was found between severe and non-severe OSA in ARD. Surprisingly, the data show that the severity of OSA correlates inversely with the ASI and ARDi. The relation between PaO2 and stiffness might be explained by a feedback mechanism that tries to overcome the reduction of aortic elasticity due to night desaturation. These findings need to be investigated in further studies with a larger study population.

Role of silodosin in patients with LUTS/BPE non responding to medical treatment with tamsulosin: a prospective, open-label, pilot study.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are frequently experienced in association with benign prostatic enlargement (BPE). Current guidelines state that alpha-blockers should be considered the first-line therapy of LUTS associated with BPE in most patients. However, in clinical practice treatment efficacy differs among individuals and, therefore, intra-class switch from one alpha-blocker to another, is frequently applied. In particular, switching to silodosin in clinical practice appears an intriguing therapeutic strategy due to the peculiar pharmacological properties of this molecule. This study evaluates the efficacy of silodosin in patients with LUTS associated with BPE who were not-responders to tamsulosin. PATIENTS AND METHODS: This was a prospective, open-label, single-center study. Patients treated with tamsulosin 0.4 mg once daily for BPE/LUTS for at least 12 months and not responding to therapy were switched to silodosin 8 mg once daily. The co-primary endpoints for evaluation of efficacy were the change in IPSS and quality of life (QoL) from the beginning of silodosin therapy to week 8. RESULTS: In total, 96 patients were enrolled. Mean International Prostatic Symptoms Score (IPSS) score at baseline was 20.0 ± 4.4, and it significantly decreased to 18.6 ± 4.5 at week 8 (mean change: -1.3 ± 1.4; 95% CI -1.6 - -1.0; p < 0.03). A decrease was also observed for the two IPSS subscores; in particular, the IPSS subscore for storage symptoms was significantly reduced at week 8, compared with baseline. A significant improvement in QoL was observed after switching to silodosin, as compared with baseline (-0.8 ± 1.0; 95% CI -1.0 - -0.6; p < 0.001). CONCLUSIONS: Silodosin improves IPSS symptoms score and QoL in patients with LUTS associated with BPE who were not-responders to tamsulosin therapy.

Assessment of the Efficiency of Consolidation Treatment through Injections of Expanding Resins by Geotechnical Tests and 3D Electrical Resistivity Tomography.

The design and execution of consolidation treatment of settled foundations by means of injection of polyurethane expanding resins require a proper investigation of the state of the foundation soil, in order to better identify anomalies responsible for the instability. To monitor the injection process, a procedure has been developed, which involves, in combination with traditional geotechnical tests, the application of a noninvasive, geophysical technique based on the electrical resistivity, which is strongly sensitive to presence of water or voids. Three-dimensional electrical resistivity tomography is a useful tool to produce effective 3D images of the foundation soils before, during, and after the injections. The achieved information allows designing the consolidation scheme and monitoring its effects on the treated volumes in real time. To better understand the complex processes induced by the treatment and to learn how variations of resistivity accompany increase of stiffness, an experiment was carried out in a full-scale test site. Injections of polyurethane expanding resin were performed as in real worksite conditions. Results confirm that the experimented approach by means of 3D resistivity imaging allows a reliable procedure of consolidation, and geotechnical tests demonstrate the increase of mechanical stiffness.

A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies.

Murine cancer models have been extremely useful for analyzing the biology of pathways involved in cancer initiation, promotion, and progression. Interestingly, several murine cancer models also exhibit heterogeneity, genomic instability and an intact immune system. However, they do not adequately represent several features that define cancer in humans, including long periods of latency, the complex biology of cancer recurrence and metastasis and outcomes to novel therapies. Therefore, additional models that better investigate the human disease are needed. In the pet population, with special references to the dog, cancer is a spontaneous disease and dogs naturally develop cancers that share many characteristics with human malignancies. More than 40 years ago, optimization of bone marrow transplantation protocols was undertaken in dogs and recently novel targeted therapies such as liposomal muramyl tripeptide phosphatidylethanolamine and several tyrosine kinase inhibitors, namely masitinib (AB1010) and toceranib phosphate (SU11654), have been developed to treat dog tumors which have then been translated to human clinical trials. In this review article, we will analyze biological data from dog tumors and comparative features with human tumors, and new therapeutic approaches translated from dog to human cancer.

Sorafenib (BAY 43-9006) in hepatocellular carcinoma patients: from discovery to clinical development.

Angiogenesis and signaling through the RAS/RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinoma (HCC). Sorafenib (Nexavar), a novel bi-aryl urea BAY 43-9006, is an orally administered multikinase inhibitor with activity against RAS/RAF kinases multikinase inhibitor with activity against RAF kinases and several receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. It is involved in angiogenic pathway and cell proliferation. Sorafenib has demonstrated potent anti-tumor activity in in vitro studies, preclinical xenograft models of different tumor types and human clinical trials. This review summarizes the history of sorafenib from its discovery by the medicinal chemistry approach through to clinical development and ongoing trials on the combination between sorafenib and trans-arterial chemoembolization (TACE) in HCC patients.

mTOR as a target of everolimus in refractory/relapsed Hodgkin lymphoma.

Despite impressive treatment advances, few options for refractory or relapsed Hodgkin Lymphoma (HL) are available and there is a need for new compounds development. A number of promising agents with multiple mechanisms of action are under investigation. Microenvironment and neoangiogenesis are acquiring a rising relevance in the pathophysiology and progression of HL. Everolimus (RAD001) is an oral antineoplastic agent derived from rapamycin, a macrocyclic lactone antibiotic, targeting the mammalian target of rapamycin (mTOR). Although the importance of mTOR signaling in the deregulated cell growth of human neoplastic cells has been recognized, this pathway is also emerging as a key regulator of the tumor response to hypoxia, as well as endothelial and stromal cells function, thereby regulating neoangiogenesis. Furthermore, mTOR plays an important role in anticancer drug resistance. The actions of everolimus within the mTOR pathway in HL result in decreased protein synthesis and cell cycle arrest, as well as in decreased angiogenesis. Everolimus has shown preliminary evidence of efficacy as a single-agent in heavily pretreated relapsed/refractory HL, with an overall fair safety profile. The purpose of this review is to discuss the employment of everolimus as an antiproliferative and antiangiogenic agent in HL and to report the critical role of the mTOR pathway and angiogenesis in this malignancy.

The pharmacological pathways of GnRH mediating the inhibition of mammary tumours: implications in humans and domestic animals.

The Gonadotropin-Releasing Hormone (GnRH) exists in two isoforms, GnRH-I and GnRH-II, in most vertebrates, including humans. Both of these isoforms and their respective receptors have been found in many healthy and pathologic extra nervous system tissues, such as cells found in cancers of the reproductive systems and, in particular, in breast cancer. GnRH analogues are used as therapeutic agents in the case of sex-hormone-dependent tumours. Besides acting as suppressors of steroidogenesis, GnRH analogues seem to interfere with mitogenic signal transduction pathways, thus behaving as negative regulators of tumour growth and progression. GnRH analogues counteract the proliferating effects of both epidermal growth factor (EGF) and insulin like growth factor (IGF-I); additionally, it affects the mitogen-activated protein kinase (MAPK) cascade and modulates the activity of the urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitory (PAI) system, which is involved in the process of metastasis. In addition, GnRH analogues decrease the expression of many growth factors involved in the development of human uterine myomas (as well as endometriotic tissue), such as the vascular endothelial growth factor (VEGF), which is deeply implied in the angiogenesis of many benign and malignant tumours, including breast cancer. Angiogenesis is one of the primary processes leading to the progression and metastasis of breast cancer cells, and a key therapeutic goal in the fight against tumours is the blocking of new vessel sprouts. Given these premises, this review provides an update on the background of anti-neoplastic properties of GnRH analogues..

VEGF concentration from plasma-activated platelets rich correlates with microvascular density and grading in canine mast cell tumour spontaneous model.

Canine cutaneous mast cell tumour (CMCT) is a common cutaneous tumour in dog, with a higher incidence than in human. CMCT is classified in three subgroups, well and intermediately differentiated (G1 and G2), corresponding to a benign disease, and poorly differentiated (G3), corresponding to a malignant disease, which metastasize to lymph nodes, liver, spleen and bone marrow. In this study, we have evaluated serum (S), platelet-poor plasma (P-PP), plasma-activated platelet rich (P-APR) and cytosol vascular endothelial growth factor (VEGF) concentrations, microvascular density (MVD) and mast cell density (MCD) in a series of 86 CMCTs and we have correlated these parameters with each other, by means of ELISA detection of VEGF and immunohistochemistry. Results show that VEGF level from cytosol P-APR and MVD were significantly higher in G3 CMCTs as compared to G1 or G2 subgroups. Moreover, a significantly strong correlation among VEGF levels from P-PAR and cytosol, MVD and MCD was found in G3 subgroup. Because VEGF levels from P-APR well correlated with MVD and malignancy grade in CMCT, we suggest that VEGF might be secreted from MCs and it may be a suitable surrogate inter-species angiogenetic markers of tumour progression in CMCT. Finally, CMCT seems to be a useful model to study the role of MCs in tumour angiogenesis and inhibition of MCs degranulation or activation might be a new anti-angiogenic strategy worthy to further investigations.

High occurrence of Helicobacter pylori in raw goat, sheep and cow milk inferred by glmM gene: a risk of food-borne infection?

Helicobacter pylori is an organism widespread in humans and sometimes responsible for serious illnesses, such as gastric and duodenal ulcers, MALToma and even gastric cancer. It has been hypothesized that the infection route by H. pylori involves multiple pathways including food-borne transmission, as the microorganism has been detected from foods such as sheep and cow milk. This work reports the results of a survey conducted in order to investigate the presence of H. pylori in raw goat, sheep and cow milk produced in Southern Italy, employing a Nested Polymerase Chain Reaction (Nested-PCR) assay for the detection of the phosphoglucosamine mutase gene (glmM), as screening method followed by conventional bacteriological isolation. Out of the 400 raw milk samples examined, 139 (34.7%) resulted positive for the presence of glmM gene, but no strains were isolated. In this work H. pylori DNA has been firstly detected from 41 (25.6%) raw goat milk samples. The results deserve further investigations on the contamination source/s of the milk samples and on the major impact that it may have on consumers.

A possible role of thymidine phosphorylase expression and 5-fluorouracil increased sensitivity in oropharyngeal cancer patients.

Thymidine Pi deoxyribosyltransferase (TP) is an enzyme involved in DNA synthesis up-regulated in tumours and it is also a pro-angiogenic factor. TP cannot activate capecitabine, because capecitabine first needs conversion by carboxylesterase and cytidine deaminase into 5-deoxy-fluorouridine. This compound can be activated by TP to 5-fluorouracil (5-FU). Although TP is not necessary for 5-FU toxicity, experimental data suggest that high levels of TP correlate with an enhanced response to 5-FU therapy. In this study, we have analysed by immunohistochemistry CD34, CD68 and TP positive cells in bioptic samples from 53 patients with T(1-3) N(0-1) M(0) oropharyngeal squamous cell carcinoma (OSC) and from 24 patients with non-dysplastic oropharyngeal leukoplakia (NDOLP). Results showed that the mean of TP-positive cells, CD68 positive macrophages and CD34 positive endothelial cells eval-uated as microvessel density (MVD) was significantly higher in OSC than in NDOLP. Moreover, at a median follow-up of 19 months, patients with TP expression and higher MVD showed a better survival rate as compared to those with low MVD, probably as a consequence of 5-FU-based therapy.We hypothesized a role for TP in oropharyngeal tumourigenesis and 5-FU activation in the adjuvant setting of OSC patients.

Is the efficacy of LDL apheresis in ischemic optic neuropathy linked to a reduction in endothelial activation markers?

Endothelial dysfunction of the optic microcirculation is considered to be the main pathogenetic mechanism in nonarteritic ischemic optic neuropathy. The aim of the present work was to assess whether a clinical improvement is correlated with a reduction in the endothelial activation markers by means of LDL apheresis (LDLA). Three weekly sessions of LDLA were administered in 23 patients affected by nonarteritic ischemic optic neuropathy. Statistically significant reductions were achieved in all parameters: total cholesterol (44.6%), LDL cholesterol (54.6%), fibrinogen (60.9%), von Willebrand factor (38.6%), sE-Selectin (22.6%), sICAM-1 (14%) and sVCAM-1 (15.5%), each of which was correlated with an improvement in the mean deviation of the visual field, although statistical significance for the single parameters was not reached. However, analysis of variance between the mean deviation improvement and the set of parameters taken together yielded highly significant results (p < 0.0001). LDLA was effective in reducing the values of all evaluated endothelial activation markers, and this trend was correlated with an improvement in the visual field.

Primary cardiac T-cell lymphoma.

Primary cardiac lymphoma (PCL), defined as a lymphoma clinically mimicking cardiac disease, with the bulk of the tumor located intrapericardially, is extremely rare in immunocompetent patients. Clinical manifestations vary depending on sites of involvement in the heart and include chest pain, arrhythmias, pericardial effusion, and heart failure. Diagnosis is often difficult and may require invasive procedures; in some cases, diagnosis is not made until autopsy. Histologically, nearly all cases of PCL reported thus far have been of B-cell origin. In this report, we describe a case of PCL of T-cell origin in an adult immunocompetent patient, the second reported in the literature to the best of our knowledge, and provide a brief overview of the features of previously published PCL cases.

Serum vascular endothelial growth factor concentrations in hepatocellular cancer patients undergoing percutaneously radiofrequency thermal ablation.

Vascular endothelial growth factor (VEGF) is known to play a central role in tumour angiogenesis. However, no data have been published with regard to the clinical-biological significance of serum (S)-VEGF in hepatocellular cancer (HCC) patients undergoing to percutaneously radiofrequency thermal ablation (PRFA). The aim of this study was to assess the modifications of S-VEGF levels in a series of 28 HCC patients in hepatitis C virus-positive cirrhosis before and after PRFA, respectively. Samples of S were taken before, 2 and 5 days after PRFA respectively and VEGF levels were assessed by ELISA. No significant difference was found between pre- and post-VEGF levels (p= n.s.; by Wilcoxon test). We suggest that S-VEGF level is not useful as early predictive marker of response to PRFA.

Radiofrequency thermal ablation of 69 lung neoplasms.

Radiofrequency thermal ablation (RFA) is a new, minimally invasive technique offered in the treatment of various neoplasms. RFA produces ionic agitation within the area to be treated, resulting in the heating of neoplastic tissue using a radiofrequency generator. Well defined areas of coagulative necrosis are formed, thereby destroying the tumor. Percutaneous CT-guided RFA was performed in 34 patients with 69 lung neoplasms. Six patients were affected by primary Non-Small Cell Lung Cancer (NSCLC), and 28 patients presented with metastatic lung nodules originating in various solid tumors. Patients were considered ineligible for surgery for the following reasons: medical comorbidities; technical reasons; severe respiratory insufficiency; refusal of surgery. Adequacy of treatment was assessed by CT-Scan and Nuclear Magnetic Resonance (NMR) with gadolinium. A median follow-up of 9 months (3-25 months) resulted in 30 patients evaluable for response with a total of 63 nodules to be treated, 58 of which achieved complete necrotic response. Relapse occurred in 5/63 treated nodules. In 2 of these patients, relapse occurred exclusively in the treated nodules, whereas in the other 3 patients, relapse occurred in the treated nodules as well as at distant sites. 9 patients are alive and disease free. Pneumothorax requiring pleural drainage was the main complication, observed in 16% of the treatment sessions. Lung RFA has shown itself to be a safe and feasible option in the treatment of lung neoplasms in patients otherwise ineligible for surgery. The high rate of complete responses obtained in our study (92%) suggests that further investigation of lung RFA, combined with chemotherapy and/or radiation therapy is warranted with the objective of improving local disease control and survival rates.

A phylogenetic comparison between acute monocytic leukemia cells and monocytes-macrophages in lower vertebrates.

In humans, monocytes and macrophages (Mphi) play a central role in immune regulation, tissue maintenance and pathogen control. In lower vertebrates, a few studies have been conducted on Mphi like cells. In acute monocytic leukemia monocytic cells, as immature cells restrained in one of the phases of their ontogenesis, would offer the opportunity to rebuild an archaic condition helpful to understand the phylogenesis. Therefore, aim of this work was to characterize in the Rainbow trout (Salmo Gairdneri Richardson) Mphi and compare them with acute leukemia monocytic cells. In the trout, Mphi's morphology is similar to that of mammals. In particular, Mphi possess an irregular embryoshaped nucleus occupying 2/3 of the cell, while the peripheral cytoplasmic profile is irregular with extroflexed plasmalemma and pseudopods. A morphological transition towards Mphi is featured by a wavy hyaline classical membrane and an irregular and extroflexed surface. Some aspects of erythrophagocytosis represented a finding of great interest indicating that the hemocatheretic function could take place directly in circulation. This condition, also observed in human acute monocytic leukemia, suggests that the information to the erythrophagocytosis is restrained under physiological conditions. Non-specific esterases, which are positive in human Mphi smear and Mphi from human lymph node tissue, were also positive in the teleost studied but with a dysomogeneous pattern. Consequently non-specific esterase system is phylogenetically conserved. A lack of immune-reactivity with the anti-CD68 monoclonal antibody (MoAb) on smear and trout tissue sections was observed. On the contrary, strong positivity was detected on human lymph node sections. In trout, the presence of Mphi and circulating Mphi like cells exhibiting an erythrocatheretic function in the circulation would indicate a primordial function that has later been replaced by the liver and the spleen.