An interband cascade laser based heterodyne detector with integrated optical amplifier and local oscillator.

Heterodyne detection based on interband cascade lasers (ICL) has been demonstrated in a wide range of different applications. However, it is still often limited to bulky tabletop systems using individual components such as dual laser setups, beam shaping elements, and discrete detectors. In this work, a versatile integrated ICL platform is investigated for tackling this issue. A RF-optimized, two-section ICL approach is employed, consisting of a short section typically used for efficient modulation of the cavity field and a long gain section. Such a laser is operated in reversed mode, with the entire Fabry-Pérot waveguide utilized as a semiconductor optical amplifier (SOA) and the electrically separated short section as detector. Furthermore, a racetrack cavity is introduced as on-chip single-mode reference generator. The field of the racetrack cavity is coupled into the SOA waveguide via an 800 nm gap. By external injection of a single mode ICL operating at the appropriate wavelength, a heterodyne beating between the on-chip reference and the injected signal can be observed on the integrated detector section of the SOA-detector.

Voltage-Gated Ion Channels: Structure, Pharmacology and Photopharmacology.

Voltage-gated ion channels are transmembrane proteins responsible for the generation and propagation of action potentials in excitable cells. Over the last decade, advancements have enabled the elucidation of crystal structures of ion channels. This progress in structural understanding, particularly in identifying the binding sites of local anesthetics, opens avenues for the design of novel compounds capable of modulating ion conduction. However, many traditional drugs lack selectivity and come with adverse side effects. The emergence of photopharmacology has provided an orthogonal way of controlling the activity of compounds, enabling the regulation of ion conduction with light. In this review, we explore the central pore region of voltage-gated sodium and potassium channels, providing insights from both structural and pharmacological perspectives. We discuss the different binding modes of synthetic compounds that can physically occlude the pore and, therefore, block ion conduction. Moreover, we examine recent advances in the photopharmacology of voltage-gated ion channels, introducing molecular approaches aimed at controlling their activity by using photosensitive drugs.

Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations.

Renewed scientific interest in psychedelic compounds represents one of the most promising avenues for addressing the current burden of mental health disorders. Classic psychedelics are a group of compounds that exhibit structural similarities to the naturally occurring neurotransmitter serotonin (5-HT). Acting on the 5-HT type 2A receptors (HT2ARs), psychedelics induce enduring neurophysiological changes that parallel their therapeutic psychological and behavioral effects. Recent preclinical evidence suggests that the ability of psychedelics to exert their action is determined by their ability to permeate the neuronal membrane to target a pool of intracellular 5-HT2ARs. In this computational study, we employ classical molecular dynamics simulations and umbrella sampling techniques to investigate the permeation behavior of 12 selected tryptamines and to characterize the interactions that drive the process. We aim at elucidating the impact of N-alkylation, indole ring substitution and positional modifications, and protonation on their membrane permeability. Dimethylation of the primary amine group and the introduction of a methoxy group at position 5 exhibited an increase in permeability. Moreover, there is a significant influence of positional substitutions on the indole groups, and the protonation of the molecules substantially increases the energy barrier at the center of the bilayer, making the compounds highly impermeable. All the information extracted from the trends predicted by the simulations can be applied in future drug design projects to develop psychedelics with enhanced activity.

Amplitude noise suppression in Yb:doped NALM oscillators utilizing saturable absorber settings.

Optical frequency combs based on fiber lasers mode-locked (ML) with a nonlinear amplifying loop mirror (NALM) have become the backbone of many cutting-edge applications, ranging from precision spectroscopy to quantum physics. Being extremely precise measurement tools, understanding their passive stability and low-noise operation regimes is vital. While several influences on the laser noise have been studied, many parameters remain poorly understood. Here, we systematically analyze under which preconditions the artificial saturable absorber settings of the laser can be modified during operation without losing mode-locking and the effects on laser noise, the spectrum and the output power. Our results show that it is possible to decrease the amplitude noise (AM noise) of the laser by more than 50 % by simply rotating a wave plate within the laser cavity. Additionally, we discuss differences to a similar effect observed in a NALM-alike laser amplifier and of changing the output coupling. These findings deepen our understanding and capabilities of optimizing the noise performance of ML fiber lasers, enable us to investigate new parameter spaces, and can be used to further optimize the noise performance of the NALM laser design, making it an ideal light source for advanced setups both in research and industry.

Effect of stacking interactions on charge transfer states in photoswitches interacting with ion channels.

The activity of ion channels can be reversibly photo-controlled via the binding of molecular photoswitches, often based on an azobenzene scaffold. Those azobenzene derivatives interact with aromatic residues of the protein via stacking interactions. In the present work, the effect of face-to-face and t-shaped stacking interactions on the excited state electronic structure of azobenzene and p-diaminoazobenzene integrated into the NaV1.4 channel is computationally investigated. The formation of a charge transfer state, caused by electron transfer from the protein to the photoswitches, is observed. This state is strongly red shifted when the interaction takes place in a face-to-face orientation and electron donating groups are present on the aromatic ring of the amino acids. The low-energy charge transfer state can interfere with the photoisomerization process after excitation to the bright state by leading to the formation of radical species.

MoBioTools: A toolkit to setup quantum mechanics/molecular mechanics calculations.

We present a toolkit that allows for the preparation of QM/MM input files from a conformational ensemble of molecular geometries. The package is currently compatible with trajectory and topology files in Amber, CHARMM, GROMACS and NAMD formats, and has the possibility to generate QM/MM input files for Gaussian (09 and 16), Orca (≥4.0), NWChem and (Open)Molcas. The toolkit can be used in command line, so that no programming experience is required, although it presents some features that can also be employed as a python application programming interface. We apply the toolkit in four situations in which different electronic-structure properties of organic molecules in the presence of a solvent or a complex biological environment are computed: the reduction potential of the nucleobases in acetonitrile, an energy decomposition analysis of tyrosine interacting with water, the absorption spectrum of an azobenzene derivative integrated into a voltage-gated ion channel, and the absorption and emission spectra of the luciferine/luciferase complex. These examples show that the toolkit can be employed in a manifold of situations for both the electronic ground state and electronically excited states. It also allows for the automatic correction of the active space in the case of CASSCF calculations on an ensemble of geometries, as it is shown for the azobenzene derivative photoswitch case.

Simple approach for extending the ambiguity-free range of dual-comb ranging.

Dual-comb (DC) ranging is an established method for high-precision and high-accuracy distance measurements. It is, however, restricted by an inherent length ambiguity and the requirement for complex control loops for comb stabilization. Here, we present a simple approach for expanding the ambiguity-free measurement length of DC ranging by exploiting the intrinsic intensity modulation of a single-cavity dual-color DC for simultaneous time-of-flight and DC distance measurements. This measurement approach enables the measurement of distances up to several hundred kilometers with the precision and accuracy of a DC interferometric setup while providing a high data acquisition rate (≈2kHz) and requiring only the repetition rate of one of the combs to be stabilized.

Five-Year Cancer Epidemiology at the National Referral Hospital: Hospital-Based Cancer Registry Data in Indonesia.

PURPOSE: In 2016, there were 1,308,061 cases of cancer being treated in Indonesia, with 2.2 trillion rupiahs spent, amounting to $486,960,633 in US dollars (purchasing power parity 2016). The high burden of cancers in Indonesia requires a valid data collection to inform future cancer-related policies. The purpose of this study is to report cancer epidemiological data from 2008 to 2012 based on Hospital-Based Cancer Registry (HBCR) data from Cipto Mangunkusumo Hospital, Indonesia. METHODS: This was a descriptive study with cross-sectional design. Data were collected from Cipto Mangunkusumo Hospital HBCR 2008-2012. Demographical, diagnostic, stages of cancer, and histopathological types of cancer data were extracted. RESULTS: After screening, 18,216 cases were included. A total of 12,438 patients were older than 39 years of age (68.3%), with a female-to-male ratio of 9:5. Most patients have cancers at advanced stages (stages III and IV, 10.2%). The most common sites of cancer were cervix uteri (2,878 cases, 15.8%), breast (2,459 cases, 13.5%), hematopoietic and reticuloendothelial systems (1,422 cases, 7.8%), nasopharynx (1,338 cases, 7.4%), and lymph nodes (1,104 cases, 6.1%). CONCLUSION: From this HBCR, cancer incidence in female was almost twice the incidence in male, largely because of the burden of cervical and breast cancers. The cervix uteri as one of the top five cancer sites based on this HBCR, 2008-2012, are still approximately consistent with Global Cancer Incidence, Mortality and Prevalence 2018, which portrayed that Indonesia has been severely afflicted by cervical cancer cases more than any other Association of Southeast Asian Nations countries. The HBCR could serve as a robust database of epidemiological data for cancer cases in Indonesia.

Binding of azobenzene and p-diaminoazobenzene to the human voltage-gated sodium channel Nav1.4.

The activity of voltage-gated ion channels can be controlled by the binding of photoswitches inside their internal cavity and subsequent light irradiation. We investigated the binding of azobenzene and p-diaminoazobenzene to the human Nav1.4 channel in the inactivated state by means of Gaussian accelerated molecular dynamics simulations and free-energy computations. Three stable binding pockets were identified for each of the two photoswitches. In all the cases, the binding is controlled by the balance between the favorable hydrophobic interactions of the ligands with the nonpolar residues of the protein and the unfavorable polar solvation energy. In addition, electrostatic interactions between the ligand and the polar aminoacids are also relevant for p-diaminoazobenzene due to the presence of the amino groups on the benzene moieties. These groups participate in hydrogen bonding in the most favorable binding pocket and in long-range electrostatic interactions in the other pockets. The thermodinamically preferred binding sites found for both photoswitches are close to the selectivity filter of the channel. Therefore, it is very likely that the binding of these ligands will induce alterations in the ion conduction through the channel.

An open-label dose escalation study evaluating tolerability and safety of a single 5-days course of temozolomide in dogs with advanced cancer.

Temozolomide is a novel oral alkylating agent that has schedule-dependent clinical activity in human malignant glioma and metastatic melanoma. Little is known about the efficacy of temozolomide in the treatment of canine solid cancers, where broad range of dosages have been used but no maximally tolerated dose (MTD) had been established. The aim of this this open-label, dose-escalating study was to determine MTD and dose-limiting toxicity (DLT) of a single temozolomide cycle in dogs with advanced solid tumours. Temozolomide was administered as a 5-days course starting at 70 mg/m2 , using escalation of 10 mg/m2 increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Safety evaluation was performed 10 days after dosing. Thirty-three client-owned dogs were enrolled. MTD was established at 150 mg/m2 and the most frequent adverse events (AEs) were hematologic and hepatic, followed by gastrointestinal, with the majority being self-resolving and of mild grade. VCOG grade 3 hepatic toxicity and grade 4 thrombocytopenia were defined as DLTs at 160 mg/m2 . A subcohort of dogs received multiple temozolomide doses on a 4-week cycle and no cumulative toxicity was documented. Conclusions of this study define temozolomide MTD at 150 mg/m2 when given once daily over 5 days. Future trials on the efficacy of temozolomide administered at its MTD are warranted.

Therapeutic management of idiopathic recurrent serositis: a retrospective study.

OBJECTIVE: Idiopathic recurrent serositis (IRS) is the most frequent serositis encountered in real-life medical sceneries, and its management represents a therapeutic challenge. There are few epidemiologic data related to IRS, though most studies have focused on recurrent pericarditis, revealing that 70% of all forms of pericarditis are idiopathic and caused by innate immunity abnormalities. The aim of this study was to evaluate outcome and recurrence rates of patients with IRS, assessing management modalities used in our Periodic Fever Centre of the Gemelli Hospital, Rome, Italy, in comparison with previous treatments in other centres. PATIENTS AND METHODS: Retrospectively, we analyzed the medical charts of 57 unselected patients with history of IRS managed during the period 1998-2017. RESULTS: A strong heterogeneity emerged by evaluating treatments of this cohort. In particular, in our Centre there was a larger use of combined therapies: 14 patients out of 27 (52%) were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, compared to only 2 patients (7.4%) previously treated with combined treatments. We used corticosteroid monotherapy only in 1 case, against 7 from other centres. The mean duration of NSAID treatment in other hospitals was 43.8 days (SD ±27.40) and 191.25 days (SD ±42.23) in our Centre; the mean duration of corticosteroid treatment in other hospitals was 101.5 days (SD ±56.40) and 180.7 days (SD ±84.87) in our Centre. Colchicine was administered in other hospitals for the same duration of NSAIDs, and corticosteroids with an average duration of 111 days (SD ±30); conversely, we administered colchicine for an average duration of 250.12 days (SD ±80.7). Relapses of IRS were reported in 1/3 of cases who had discontinued therapies. CONCLUSIONS: The overall duration of treatments to manage IRS has a weight in terms of patients' outcome. A reduced duration of therapy with corticosteroids and a longer duration of therapy with NSAIDs determine a longer disease-free interval. A significant discriminating effect in terms of risk of IRS recurrence relies in an earlier combination therapy with colchicine independently from the start with either NSAIDs or corticosteroids. Finally, the evaluation of genes causing autoinflammatory diseases has not revealed any pathogenetic variants in a subcohort of 20/57 patients with IRS.

Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons.

AIMS: The crucial step in the pathogenic events that lead to the development and the progression of multiple sclerosis (MS) is the infiltration of autoreactive T cells in the brain. Data from experimental autoimmune encephalomyelitis (EAE) mice indicate that, together with microglia, T cells are responsible for the enhancement of the glutamatergic transmission in central neurons, contributing to glutamate-mediated excitotoxicity, a pathological hallmark of both EAE and MS brains. Here, we addressed the synaptic role of T cells taken from MS patients. METHODS: A chimeric model of human T cells and murine brain slices was established to record, by Patch Clamp technique, the glutamatergic transmission in the presence of T cells isolated from the peripheral blood of healthy subjects (HS), active (a) and nonactive (na) relapsing remitting MS patients. Intracellular staining and flow cytometry were used to assess tumour necrosis factor (TNF) expression in T cells. RESULTS: Chimeric experiments indicated that, compared to HS and naMS, T cells from aMS induced an increase in glutamatergic kinetic properties of striatal neurons. Such alteration, reminiscent of the those induced by EAE T cells, was blocked by incubation of the slices with etanercept, a TNF receptor antagonist. Of note, T cells from aMS expressed more TNF than naMS patients and HS subjects. CONCLUSION: These data highlight the synaptotoxic potential retained by MS T cells, suggesting that during the inflammatory phase of the disease infiltrating T cells could influence the neuronal activity contributing to the TNF-mediated mechanisms of glutamate excitotoxicity in central neurons.

A magnetar-powered X-ray transient as the aftermath of a binary neutron-star merger.

Mergers of neutron stars are known to be associated with short γ-ray bursts1-4. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field5-8 (that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts9,10. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst11,12. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown13. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf13. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref. 14). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do15,16. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.

Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma.

Canine malignant melanoma (MM) is a highly aggressive tumour with a low survival rate and represents an ideal spontaneous model for the human counterpart. Considerable progress has been recently obtained, but the therapeutic success for canine melanoma is still challenging. Little is known about the mechanisms beyond pathogenesis and melanoma development, and the molecular response to radiotherapy has never been explored before. A faster and deeper understanding of cancer mutational processes and developing mechanisms are now possible through next generation sequencing technologies. In this study, we matched whole exome and transcriptome sequencing in four dogs affected by MM at diagnosis and at disease progression to identify possible genetic mechanisms associated with therapy failure. According to previous studies, a genetic similarity between canine MM and its human counterpart was observed. Several somatic mutations were functionally related to MAPK, PI3K/AKT and p53 signalling pathways, but located in genes other than BRAF, RAS and KIT. At disease progression, several mutations were related to therapy effects. Natural killer cell-mediated cytotoxicity and several immune-system-related pathways resulted activated opening a new scenario on the microenvironment in this tumour. In conclusion, this study suggests a potential role of the immune system associated to radiotherapy in canine melanoma, but a larger sample size associated with functional studies are needed.

Comparison of definitive-intent finely fractionated and palliative-intent coarsely fractionated radiotherapy as adjuvant treatment of feline microscopic injection-site sarcoma.

OBJECTIVES: The aim of this retrospective, bi-institutional study was to evaluate the progression-free interval in a cohort of cats with postoperative microscopic injection-site sarcoma (ISS) treated with two different radiotherapy protocols. METHODS: Included in the study were cats with ISSs undergoing macroscopic surgical removal and subsequent electron beam radiotherapy treatment with either a finely fractionated protocol (48 or 52.8 Gy over 4 weeks delivered in 12 or 16 fractions) or a coarsely fractionated protocol (36 Gy over 3 weeks administered in six fractions). Medical records were reviewed and follow-up information was collected. The Kaplan-Meier method and log-rank test were used to compare the progression-free interval (PFI) between the two protocols and to test the influence of many clinical variables. RESULTS: Fifty-nine cats were included; 38 underwent a finely fractionated protocol and 21 a coarsely fractionated protocol. PFI was not significantly different between the two groups. Overall PFI was 2000 days (2000 vs 540 days; P = 0.449). When only first-occurrence cases were included, median PFI was significantly longer in the finely fractionated group compared with the coarsely fractionated group (1430 vs 540 days; P = 0.007). In cats that underwent multiple surgeries PFI was not different between protocols (233 vs 395 days; P = 0.353). CONCLUSIONS AND RELEVANCE: Cats with first-occurrence ISSs appear to benefit from postoperative finely fractionated radiotherapy. The same benefit was not evident in cats that underwent multiple surgeries and we think a coarsely fractionated protocol would be indicated in these cases.

Steroids and Survival in Critically Ill Adult Patients: A Meta-analysis of 135 Randomized Trials.

OBJECTIVE: Corticosteroids have important effects on intermediate outcomes in critically ill patients, but their effect on survival is unknown. The objective of this meta-analysis was to analyze the effect on mortality of corticosteroids in critical and perioperative settings. DESIGN: A meta-analysis of randomized trials. SETTING: PubMed, Embase, BioMed Central, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched to February 1, 2018, for randomized trials comparing corticosteroids with placebo or standard care. PARTICIPANTS: Critically ill or surgical adult patients. INTERVENTIONS: Corticosteroids compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: A total of 44,553 patients from 135 studies were included. Overall, mortality in the corticosteroid group and in the control group were similar (16% v 16%; p = 0.9). Subanalyses identified a beneficial effect of corticosteroids on survival in patients with respiratory system diseases (9% v 13%; p < 0.001) and bacterial meningitis (28% v 32%; p= 0.04), and a detrimental effect on survival in patients with traumatic brain injury (22% v 19%; p < 0.001). No differences in mortality were found in patients with cardiac diseases (7% v 6%; p = 0.7), in patients undergoing cardiac surgery (2.8% v 3.2% p = 0.14), and when treatment duration or patient age were considered. CONCLUSIONS: This meta-analysis documents the safety of corticosteroids in the overall critically ill population with the notable exception of brain injury patients, a setting where the authors confirmed their detrimental effect on survival. A possible beneficial effect of corticosteroids on survival was found among patients with respiratory diseases and in patients with bacterial meningitis.

A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum.

The N-palmitoylethanolamine (PEA) is an endogenous member of the endocannabinoid system (ECS) with several biological functions, including a neuromodulatory activity in the central nervous system. To shed light on the neuronal function of PEA, we investigated its involvement in the control of both excitatory and inhibitory transmission in the murine striatum, a brain region strongly modulated by the ECS. By means of electrophysiological recordings, we showed that PEA modulates inhibitory synaptic transmission, through activation of GPR55 receptors, promoting a transient increase of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency. The subsequently rundown effect on sIPSC frequency was secondary to the delayed stimulation of presynaptic cannabinoid CB1 receptors (CB1Rs) by the endocannabinoid 2-AG, whose synthesis was stimulated by PEA on postsynaptic neurons. Our results indicate that PEA, acting on GPR55, enhances GABA transmission in the striatum, and triggers a parallel synthesis of 2-AG at the postsynaptic site, that in turn acts in a retrograde manner to inhibit GABA release through the stimulation of presynaptic CB1Rs. This electrophysiological study identifies a previously unrecognized function of PEA and of GPR55, demonstrating that GABAergic transmission is under the control of this compound and revealing that PEA modulates the release of the endocannabinoid 2-AG.

microRNAs Modulate Spatial Memory in the Hippocampus and in the Ventral Striatum in a Region-Specific Manner.

MicroRNAs are endogenous, noncoding RNAs crucial for the post-transcriptional regulation of gene expression. Their role in spatial memory formation, however, is poorly explored. In this study, we analyzed learning-induced microRNA expression in the hippocampus and in the ventral striatum. Among miRNAs specifically downregulated by spatial training, we focused on the hippocampus-specific miR-324-5p and the ventral striatum-specific miR-24. In vivo overexpression of the two miRNAs demonstrated that miR-324-5p is able to impair memory if administered in the hippocampus but not in the ventral striatum, while the opposite is true for miR-24. Overall, these findings demonstrate a causal relationship between miRNA expression changes and spatial memory formation. Furthermore, they provide support for a regional dissociation in the post-transcriptional processes underlying spatial memory in the two brain structures analyzed.

HYPOFRACTIONATED RADIOTHERAPY FOR MACROSCOPIC CANINE SOFT TISSUE SARCOMA: A RETROSPECTIVE STUDY OF 50 CASES TREATED WITH A 5 × 6 GY PROTOCOL WITH OR WITHOUT METRONOMIC CHEMOTHERAPY.

Wide surgical resection or a marginal/incomplete resection followed by full-course radiation therapy is the current standard of care for canine soft tissue sarcoma. The purpose of this retrospective, descriptive, bi-institutional study was to determine the effectiveness and toxicity of a hypofractionated 5 × 6 Gy protocol on macroscopic canine soft tissue sarcoma in terms of progression-free interval (PFI) and overall survival (OS), and to identify prognostic factors for patient outcome. Dogs with macroscopic soft tissue sarcoma irradiated with 5 × 6 Gy were eligible for the study. Progression-free interval and OS were compared with respect to different tumor and patient characteristics by the Kaplan-Meier method and multivariable Cox regression analysis. Fifty dogs with macroscopic disease were included. All dogs received the same radiation therapy protocol; part of the group (n = 20) received postradiation metronomic chemotherapy. Median PFI for all cases was 419 days (95% confidence interval (CI): 287-551) and median OS was 513 days (95% CI: 368-658). Dogs with tumors on the limbs had significantly longer PFI and OS, compared with head or trunk. Increasing tumor burden decreased OS. The addition of metronomic chemotherapy yielded a significantly longer OS (757 days (95% CI: 570-944) compared with dogs that did not receive systemic treatment (286 days (95% CI: 0-518), (P = 0.023)), but did not influence progression-free interval. Toxicity was low throughout all treatments. The 5 × 6 Gy radiation therapy protocol was well tolerated and provided long PFI and OS in dogs with macroscopic soft tissue sarcoma.

Combination of radiation therapy and firocoxib for the treatment of canine nasal carcinoma.

Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.