Extended nodal radiotherapy for prostate cancer relapse guided with [11C]-choline PET/CT: ten-year results in patients enrolled in a prospective trial.

AIMS: To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and [11C]-choline positron emission tomography (PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs). METHODS: From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8 Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5 Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months. RESULTS: Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis. CONCLUSIONS: In PC relapsed patients treated with ENRT and [11C]-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67 months and OS of 110 months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.

Observation of Collider Muon Neutrinos with the SND@LHC Experiment.

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at sqrt[s]=13.6 TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.8 fb^{-1}. The search is based on information from the active electronic components of the SND@LHC detector, which covers the pseudorapidity region of 7.2<η<8.4, inaccessible to the other experiments at the collider. Muon neutrino candidates are identified through their charged-current interaction topology, with a track propagating through the entire length of the muon detector. After selection cuts, 8 ν_{µ} interaction candidate events remain with an estimated background of 0.086 events, yielding a significance of about 7 standard deviations for the observed ν_{µ} signal.

Final Results of the OPERA Experiment on ν_{τ} Appearance in the CNGS Neutrino Beam.

The OPERA experiment was designed to study ν_{µ}→ν_{τ} oscillations in the appearance mode in the CERN to Gran Sasso Neutrino beam (CNGS). In this Letter, we report the final analysis of the full data sample collected between 2008 and 2012, corresponding to 17.97×10^{19} protons on target. Selection criteria looser than in previous analyses have produced ten ν_{τ} candidate events, thus reducing the statistical uncertainty in the measurement of the oscillation parameters and of ν_{τ} properties. A multivariate approach for event identification has been applied to the candidate events and the discovery of ν_{τ} appearance is confirmed with an improved significance level of 6.1σ. |Δm_{32}^{2}| has been measured, in appearance mode, with an accuracy of 20%. The measurement of the ν_{τ} charged-current cross section, for the first time with a negligible contamination from ν[over ¯]_{τ}, and the first direct evidence for the ν_{τ} lepton number are also reported.

Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.

The OPERA experiment was designed to search for ν_{µ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions. The experiment took data from 2008 to 2012 in the CERN Neutrinos to Gran Sasso beam. The observation of the ν_{µ}→ν_{τ} appearance, achieved with four candidate events in a subsample of the data, was previously reported. In this Letter, a fifth ν_{τ} candidate event, found in an enlarged data sample, is described. Together with a further reduction of the expected background, the candidate events detected so far allow us to assess the discovery of ν_{µ}→ν_{τ} oscillations in appearance mode with a significance larger than 5σ.

Androgens and estrogens prevent rosiglitazone-induced adipogenesis in human mesenchymal stem cells.

Thiazolidinediones (TZD), a class of anti-diabetic drugs, determine bone loss and increase fractures particularly in post-menopausal women, thus suggesting a protective role of sex steroids. We have previously demonstrated that the TZD rosiglitazone (RGZ) negatively affects bone mass by inhibiting osteoblastogenesis, yet inducing adipogenesis, in bone marrow-derived human mesenchymal stem cells (hMSC). The aim of this study was to determine whether estrogens and androgens are able to revert the effects of RGZ on bone. hMSC express estrogen receptor α and ß and the androgen receptor. We found that 17ß-estradiol (10 nM), the phytoestrogen genistein (10 nM), testosterone (10 nM) and the non-aromatizable androgens dihydrotestosterone (10 nM) and methyltrienolone (10 nM) effectively counteracted the adipogenic effect of RGZ (1 µM) in hMSC induced to differentiate into adipocytes, as determined by evaluating the expression of the adipogenic marker peroxisome proliferator-activated receptor γ and the percentage of fat cells. Furthermore, when hMSC were induced to differentiate into osteoblasts, all the above-mentioned molecules and also quercetin, another phytoestrogen, significantly reverted the inhibitory effect of RGZ on the expression of the osteogenic marker osteocalcin and decreased the number of fat cells observed after RGZ exposure. Our study represents, to our knowledge, the first demonstration in hMSC that androgens, independently of their aromatization, and estrogens are able to counteract the negative effects of RGZ on bone. Our data, yet preliminary, suggest the possibility to try to prevent the negative effects of TZD on bone, using steroid receptor modulators, such as plant-derived phytoestrogens, which lack evident adverse effects.

Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

OPERA tau neutrino charged current interactions.

The OPERA experiment was designed to discover the vτ appearance in a vµ beam, due to neutrino oscillations. The detector, located in the underground Gran Sasso Laboratory, consisted of a nuclear photographic emulsion/lead target with a mass of about 1.25 kt, complemented by electronic detectors. It was exposed from 2008 to 2012 to the CNGS beam: an almost pure vµ beam with a baseline of 730 km, collecting a total of 1.8·1020 protons on target. The OPERA Collaboration eventually assessed the discovery of vµâ†’vτ oscillations with a statistical significance of 6.1 σ by observing ten vτ CC interaction candidates. These events have been published on the Open Data Portal at CERN. This paper provides a detailed description of the vτ data sample to make it usable by the whole community.

In vivo effects of rosiglitazone in a human neuroblastoma xenograft.

BACKGROUND: Neuroblastoma (NB) is the most common extra-cranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. There is in vitro evidence that the peroxisome proliferator-activated receptor gamma (PPARgamma) might be a target for pharmacological intervention in NB. We have previously demonstrated that the PPARgamma agonist rosiglitazone (RGZ) exerts strong anti-tumoural effects in the human NB cell line, SK-N-AS. The aim of this study was to evaluate whether RGZ maintains its anti-tumoural effects against SK-N-AS NB cells in vivo. METHODS AND RESULTS: For this purpose, tumour cells were subcutaneously implanted in nude mice, and RGZ (150 mg kg(-1)) was administered by gavage daily for 4 weeks. At the end of treatment, a significant tumour weight inhibition (70%) was observed in RGZ-treated mice compared with control mice. The inhibition of tumour growth was supported by a strong anti-angiogenic activity, as assessed by CD-31 immunostaining in tumour samples. The number of apoptotic cells, as determined by cleaved caspase-3 immunostaining, seemed lower in RGZ-treated animals at the end of the treatment period than in control mice, likely because of the large tumour size observed in the latter group. CONCLUSIONS: To our knowledge, this is the first demonstration that RGZ effectively inhibits tumour growth in a human NB xenograft and our results suggest that PPARgamma agonists may have a role in anti-tumoural strategies against NB.

Test of "crab-waist" collisions at the DAPhiNE Phi factory.

The electron-positron collider DAPhiNE, the Italian Phi factory, has been recently upgraded in order to implement an innovative collision scheme based on large crossing angle, small beam sizes at the crossing point, and compensation of beam-beam interaction by means of sextupole pairs creating a "crab-waist" configuration in the interaction region. Experimental tests of the novel scheme exhibited an increase by a factor of 3 in the peak luminosity of the collider with respect to the performances reached before the upgrade. In this Letter we present the new collision scheme, discuss its advantages, describe the hardware modifications realized for the upgrade, and report the results of the experimental tests carried out during commissioning of the machine in the new configuration and standard operation for the users.

Immunomodulatory effects of BXL-01-0029, a less hypercalcemic vitamin D analogue, in human cardiomyocytes and T cells.

Current immunosuppressive protocols have reduced rejection occurrence in heart transplantation; nevertheless, management of heart transplant recipients is accompanied by major adverse effects, due to drug doses close to toxic range. In allograft rejection, characterized by T-helper 1 (Th1) cell-mediated response, the CXCL10-CXCR3 axis plays a pivotal role in triggering a self-promoting inflammatory loop. Indeed, CXCL10 intragraft production, required for initiation and development of graft failure, supports organ infiltration by Th1 cells. Thus, targeting the CXCL10-CXCR3 axis while avoiding generalized immunosuppression, may be of therapeutic significance. Based on preclinical evidence for immunoregulatory properties of vitamin D receptor agonists, we propose that a less hypercalcemic vitamin D analogue, BXL-01-0029, might have the potential to contribute to rejection management. We investigated the effect of BXL-01-0029 on CXCL10 secretion induced by proinflammatory stimuli, both in human isolated cardiomyocytes (Hfcm) and purified CD4+ T cells. Mycophenolic acid (MPA), the active agent of mycophenolate mofetil, was used for comparison. BXL-01-0029 inhibited IFNgamma and TNFalpha-induced CXCL10 secretion by Hfcm more potently than MPA, impairing cytokine synergy and pathways. BXL-01-0029 reduced also CXCL10 protein secretion and gene expression by CD4+ T cells. Furthermore, BXL-01-0029 did not exert any toxic effect onto both cell types, suggesting its possible use as a dose-reducing agent for conventional immunosuppressive drugs in clinical transplantation.

A single-institution restrospective experience of brachytherapy in the treatment of pituitary tumors: transsphenoidal approach combined with (192)Ir-afterloading catheters.

BACKGROUND AND AIM: Radiotherapy may be used as an adjuvant treatment of pituitary adenomas. The aim of our study was to present our experience of multimodal treatment of pituitary adenomas, consisting in temporary implantation of (192)Ir-labeled wires following transphenoidal surgery. SUBJECTS AND METHODS: An observational investigation was performed on a series of 80 patients undergoing surgery (S) for pituitary adenomas between 1982 and 2000, some of whom received post-operative external beam radiotherapy (EBRT) (no.=19 between 1982 and 1990), brachytherapy (B) (no.=35, all after 1991), or both irradiation modalities (EBRT+B) (no.=14). The different treatments were compared in terms of hormonal normalization in the subgroup of patients with hypersecreting adenomas, tumor control, and side effects. RESULTS: Hormonal normalization was obtained in 84% of S+B patients and in 61% of S+EBRT patients. Tumor control was obtained in 74.3% of S+B patients and in 63.1% of S+EBRT patients. Anterior pituitary hormones deficits ranged from 8.6-34% in S+B patients and from 15.8-47.4% in S+EBRT patients, after a mean follow-up of 14 yr. The latter group also showed a higher rate of multiple deficits (42.1% vs 22.8%). Diabetes insipidus and other major complications were rare events in all groups. CONCLUSIONS: We presented one original experience regarding brachytherapy in the management of pituitary tumors, which turned out to be effective and safe. Additional prospective, and possibly randomized, studies should clarify whether in the era of 3-dimensional conformal radiotherapy and stereotactic radiotherapy this treatment modality may still have a role.

Effects of topical gluco-oligosaccharide and collagen tripeptide F in the treatment of sensitive atopic skin.

Sensitive skin is a dermatological problem of increasing incidence in western countries and is sometimes associated with atopic condition and bacterial sovrainfection. The purpose of this study is to evaluate in a double blind, randomized, placebo controlled trial the efficacy of gluco-oligosaccharide and collagen tripeptide F in controlling the signs and symptoms of sensitive atopic skin. Forty female subjects (age, 30-59 years) affected by non-lesional atopic sensitive skin entered the study. Skin sensitivity was determined by a dermatologist on the basis of medical history, stinging test, dermatological examination and a questionnaire. A treatment with the test products (active and placebo) was carried out for 4 weeks. Measurements and clinical evaluation were carried out at baseline and at the end of the study. The following objective parameters investigated were bacterial count, skin pH and colour, transepidermal water loss (TEWL), stratum corneum hydration, skin roughness and mechanical properties. Clinical assessment included also a scoring system for dryness, desquamation, irritation, erythema and papules. Significant differences were found in the active treated group when compared with the placebo and in particular for instrumental parameters of roughness (P < 0.02), volume (P < 0.01), TEWL (P < 0.02), erythema (P < 0.0006) and clinical parameters of dryness, desquamation and irritation (P < 0.001). Moisturization levels and skin colour improved significantly in both the active and placebo groups. In conclusion, the study shows that the modulation of bacterial proliferation and normalization of skin barrier properties and stratum corneum moisturization can improve the symptoms of sensitive skin.

Unconventional secretion of α-Crystallin B requires the Autophagic pathway and is controlled by phosphorylation of its serine 59 residue.

α-Crystallin B (CRYAB or HspB5) is a chaperone member of the small heat-shock protein family that prevents aggregation of many cytosolic client proteins by means of its ATP-independent holdase activity. Surprisingly, several reports show that CRYAB exerts a protective role also extracellularly, and it has been recently demonstrated that CRYAB is secreted from human retinal pigment epithelial cells by an unconventional secretion pathway that involves multi-vesicular bodies. Here we show that autophagy is crucial for this unconventional secretion pathway and that phosphorylation at serine 59 residue regulates CRYAB secretion by inhibiting its recruitment to the autophagosomes. In addition, we found that autophagosomes containing CRYAB are not able to fuse with lysosomes. Therefore, CRYAB is capable to highjack and divert autophagosomes toward the exocytic pathway, inhibiting their canonical route leading to the lysosomal compartment. Potential implications of these findings in the context of disease-associated mutant proteins turn-over are discussed.

Elocalcitol inhibits inflammatory responses in human thyroid cells and T cells.

T-helper 1 (Th1) cell-mediated inflammatory responses predominate in the early pathogenesis of Graves' disease (GD), whereas Th2 cell-mediated immunity may play a role in later stages. The chemokine CXCL10 and its receptor CXCR3 are expressed in most thyroid glands of early GD patients. Circulating CXCL10 levels inversely correlate with disease duration; CXCL10 maximal expression also correlates with interferon (IFN)gamma levels in recent GD onset. Methimazole (MMI) reduces CXCL10 secretion by isolated thyrocytes, decreases serum CXCL10 levels, and promotes a transition from Th1 to Th2 dominance in patients in GD active phase. Vitamin D receptor agonists exhibit antiinflammatory properties and promote tolerance induction. We investigated the effects and the mechanism of action of a nonhypercalcemic vitamin D receptor agonist, elocalcitol (BXL-628), compared with MMI on CXCL10 secretion induced by proinflammatory cytokines. Furthermore, we studied the effects of both drugs on Th1, Th17, and Th2 cytokine secretion in CD4+ T cells. ELISA, cytometry, immunocytochemistry, Western blot, and quantitative real-time PCR were used for protein and gene analysis. In human thyrocytes, elocalcitol inhibited IFNgamma and TNFalpha-induced CXCL10 protein secretion more potently than MMI. Elocalcitol impaired both cytokine intracellular pathways, whereas MMI was effective only on the IFNgamma pathway. In CD4+ T cells, elocalcitol decreased Th1- and Th17-type cytokines, and promoted Th2-type cytokine secretion. Elocalcitol and MMI inhibited Th1 cytokine-mediated responses in thyrocytes and CD4+ T cells. In addition, elocalcitol promoted a shift toward a Th2 response. In conclusion, elocalcitol could represent a novel pharmacological tool in the treatment of autoimmune thyroid diseases.

The Y606C RET mutation causes a receptor gain of function.

CONTEXT: Medullary thyroid carcinoma (MTC) is the most common feature of multiple endocrine neoplasia type 2A (MEN2A) and occurs in almost all patients affected by germline RET mutations. OBJECTIVE: We identified and characterized an activating germline RET point mutation (G>A substitution leading to the heterozygous missense mutation Y606C in exon 10), in a 58-year-old female affected by MTC. DESIGN: The RET/Y606C and RET/C620Y, obtained by site-directed mutagenesis, as well as the RET/wild-type (wt) were cloned in an expression vector and transiently transfected in NIH3T3 fibroblasts. In vitro cell model was used to evaluate the effect of Y606C mutation on the RET downstream signalling pathways through Western blot analysis. RESULTS: We found that the cysteine insertion, due to the Y606C mutation, results in increased receptor dimerization, which is accompanied by an increased tyrosine phosphorylation of the Y905 residue in the RET/Y606C, demonstrating that the Y606C mutation is associated with constitutive receptor activation. As RET activation results in an intracellular signalling cascade involving extracellular signal-regulated kinases (ERKs), we investigated ERK activity in our transfected cells. Results demonstrated a significant increase in ERK2 phosphorylation in the RET/Y606C vs. the RET/wt and RET/C620Y transfected cells, suggesting an up-regulation of RET signalling. CONCLUSIONS: All these findings demonstrate that the Y606C mutation is associated with RET constitutive activation and thus has to be considered of pathogenetic relevance in the development of MTC.

The critical role of SDF-1/CXCR4 axis in cancer and cancer stem cells metastasis.

Chemokines exert their multifunctional role in several physiologic and pathologic processes through interaction with their specific receptors. Much evidence have revealed that metastatic spread tumor cells may use chemokine-mediated mechanisms. In particular, an involvement of stromal cell-derived factor-1 (SDF-1) in growth of primary tumors and in metastatic process has been demonstrated. Indeed, it has been suggested that CXCR4 expression by tumor cells, plays a critical role in cell metastasis by a chemotactic gradient to organs expressing the ligand SDF-1. Moreover, CXCR4 overexpression correlated with poor prognosis in many types of cancer. In physiologic condition, SDF-1 also plays an essential role modulating stem cell proliferation, survival, and homing through its canonical receptor CXCR4. Recently, several studies have demonstrated the existence of a small subset of cancer cells which share many characteristics with stem cells and named cancer stem cells (CSC). They constitute a reservoir of self-sustaining cells with the ability to maintain the tumor growth. In particular, most of them express CXCR4 receptor and respond to a chemotactic gradient of its specific ligand SDF-1, suggesting that CSC probably represent a subpopulation capable of initiating metastasis. This review focuses on the role of SDF-1/CXCR4 axis in cancer and in the metastatic progression by tumoral cells, as well as the role of CSC in tumor pathogenesis and in metastatic process. A better understanding of migratory mechanism involving cancer cells and CSC provides a powerful tool for developing novel therapies reducing both local and distant recurrences.

Endometrial metastasis of a primitive neuroendocrine ovarian carcinoma: management and treatment of a case.

BACKGROUND: Neuroendocrine tumours are a heterogeneous group of separate clinico-pathological entities which have a common characteristic, i.e., expression of potential endocrine differentiation. In the ovary, the term "neuroendocrine" relates mainly to widely known carcinoids, but it may also be applied to rare neuroendocrine carcinomas as non-small cell type and small cell carcinomas of pulmonary type. In the literature only 11 cases of primary ovarian non-small cell neurendocrine carcinomas have been described and ten of these were associated with a surface epithelial ovarian tumour. Small cell neuroendocrine carcinoma of the ovary is a rare malignant tumour of the ovary. Advanced small cell carcinoma of the ovary is a very aggressive tumour with an overall poor prognosis and unfavourable outcome. CASE REPORT: The case reported is unique in the literature because the authors describe a rare case of endometrial metastasis of a primary ovarian non-small cell neurendocrine carcinoma without any surface epithelial ovarian tumour association. The tumour invaded up to less than half of the myometrium. The first symptoms were related to endometrial metastasis as metrorrhagia and pelvic pain while the asymptomatic presence of primary ovarian carcinoma was not acknowledged with physical examination, routine biochemistry, tumour markers, blood count and traditional transvaginal greyscale ultrasound. CONCLUSION: Magnetic resonance and three-dimensional (3D) ultrasonography with power Doppler are a great help in the diagnosis of ovarian localisation but only immunohistochemistry on histological material can provide a correct diagnosis. Immunohistochemistry expression of Ki67 is a useful marker of malignancy. Due to the rarity of this neoplasm, a general consensus for optimal treatment has yet to emerge. The reported biological aggressiveness of these tumours prompts combined treatment with radical surgery and adjuvant polychemotherapy.

Characterization of sustainable polyhydroxyls, produced from bio-based feedstock, and polyurethane and copolymer urethane-amide foams.

This manuscript presents data related to the research article entitled "Synthesis and characterization of sustainable polyurethane foams based on polyhydroxyls with different terminal groups" (DOI: 10.1016/j.polymer.2018.06.077) [1]. We provide Supplementary data on the chemical properties, in terms of FTIR characterization, of polyhydroxyls produced starting from bio-based feedstock (biosuccinic acid and 1,4 butandiol) and thermal properties (glass transition temperature-Tg and thermal degradation behavior) of polyurethane and copolymer urethane-amide foams manufactured from the aforementioned polyhydroxyls. The FTIR characterization elucidates the chemical structure of polyhydroxyls and allows to make some hypothesis on their reaction routes with the isocyanate molecules. The thermal characterization revealed that the addition of bio-based polyhydroxyls to the sample formulations improves both the glass transition and degradation temperature of the foams. These foamed products exhibit potential performances to be applied as a substitute for conventional polyurethane foams.

Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity.

Endothelial cell receptors for the angiostatic chemokines IFN-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by IFN-gamma (Mig) have not yet been identified, and the mechanisms responsible for the effects of these chemokines on angiogenesis are still unclear. IP-10 and Mig share a common functional receptor on activated T lymphocytes, named CXC chemokine receptor 3 (CXCR3). Using in situ hybridization and immunohistochemistry, we show that CXCR3 is expressed by a small percentage of microvascular endothelial cells in several human normal and pathological tissues. Primary cultures of human microvascular endothelial cells (HMVECs) likewise express CXCR3, although this expression is limited to the S/G2-M phase of their cell cycle. Both IP-10 and Mig, as well as the IFN-gamma-inducible T-cell alpha chemoattractant (I-TAC), which all share high-affinity binding for CXCR3, block HMVEC proliferation in vitro, an effect that can be inhibited by an anti-CXCR3 antibody. These data provide definitive evidence of CXCR3 expression by HMVEC and open new avenues for therapeutic interventions in all conditions in which an angiostatic effect may be beneficial.