Outcomes of Treatment of Eyelids and Third Eyelid Tumours in Dogs Using High-Frequency Radiowave Surgery.

In human ophthalmology, the benefits of using high-frequency radiowave (HFR) electrocautery for surgical procedures were demonstrated and include effective haemostasis, shorter surgery times, and rapid recovery. In canine eyelid surgery, intraoperative bleeding is a common feature that may obscure the surgical field view and lead to the increased swelling of adjacent tissues, bruising, and pain. To evaluate the efficacy and benefits of HFR electrocautery in canine eyelid and third eyelid surgery, the medical records of 48 surgical excisions of eyelid tumours (involving up to one-third of the eyelid length) and 4 third eyelid excisions were reviewed. The information was collected including the breed, age, clinical signs, HFR power setting and mode of the surgical unit, electrode used for the surgery, intraoperative complications, histopathological diagnosis, and postoperative outcomes. Surgical techniques were performed using the Surgitron Dual 3.8 MHz Frequency RF device (Ellman International, Oceanside, NY, USA). Intraoperative bleeding was recorded as absent or very mild, and the surgical procedures were very fast. No complications occurred during the procedures. Healing within 10 days was observed in all the dogs. No tumour recurrences were recorded at the 12-month follow-up. HFR electrosurgery proved to be a safe, effective, and easy-to-perform technique for the removal of eyelid and third eyelid tumours in dogs.

Incorporation of Testicular Ultrasonography and Hair Steroid Concentrations in Bull Breeding Soundness Evaluation.

Testicular ultrasonography and steroid concentrations (cortisol, dehydroepiandrosterone sulfate (DHEA-S), cortisol/DHEA-S ratio, testosterone) in hair were examined for their utility in the bull breeding soundness evaluation (BBSE). Beef and dairy bulls (n = 16; 2.7 ± 0.4 years old; body condition score 3.2 ± 0.1) of five breeds were maintained under the same conditions at an accredited semen collection center. Bulls underwent routine semen collection twice weekly for 12 weeks and semen was processed and cryopreserved. Ultrasonography and hair sampling were undertaken at the last semen collection. Bulls with homogeneous testicular parenchyma (n = 8) had a higher (p < 0.05) percentage of motile sperm post-thawing compared with bulls with heterogeneous parenchyma (n = 8). There were no differences (p > 0.05) in the hair concentrations of cortisol, DHEA-S, and testosterone between bulls with homogeneous and heterogeneous parenchyma. In bulls with homogeneous parenchyma, hair DHEA-S concentration was positively correlated with percentage motile sperm (R2 = 0.76), progressively motile sperm (R2 = 0.70), and motility yield (R2 = 0.71). The findings indicate that the integration of testicular ultrasonography and hair DHEA-S status in the BBSE could provide a more comprehensive assessment of indicative fertility in bulls. Additionally, ultrasonography can be used in the BBSE when the evaluation of semen parameters is not available.

Computed Tomographic Assessment of Pituitary Gland Dimensions in Domestic Short-Haired Cats.

The detection of subtle changes in the pituitary dimensions has relevant clinical implications. In cats, a few studies have established the cut-off values of the pituitary gland's dimensions using small and inhomogeneous samples. The aims of this study were: to determine by computed tomography (CT) the pituitary linear dimensions and the pituitary-to-brain (P:B) ratio in a sample of domestic short-haired (DSH) cats; to assess the effects of sex, age, and weight on pituitary dimensions; and to evaluate the inter- and intra-observer agreement for such measurements. All skull CTs of DSH cats performed over four years using a multidetector CT and a standardized protocol were retrospectively reviewed. The exclusion criteria were: clinical, laboratory, or CT alterations of the pituitary gland, brain diseases, fractures of the neurocranium, and diabetes. The pituitary dimensions and brain area were assessed by two different observers using multiplanar reconstructions and automated segmentation tools. Fifty-one cats were included in the final sample. The intraclass correlation coefficients for intra- and inter-observer reliability were good/excellent, and moderate/good, respectively. No differences between sexes were detected, and negligible correlations were found between age and weight. According to this study, a pituitary gland with a height > 4 mm or a P:B ratio > 0.49 mm should be considered enlarged.

Pregnancies following Protocols for Repetitive Synchronization of Ovulation in Primiparous Buffaloes in Different Seasons.

Primiparous buffaloes were tested in two periods of the year characterized, by either low or high reproductive efficiency. They were subjected to two protocols for synchronization of ovulation: (i) Ovsynch (OV) and (ii) progesterone based (P4) treatment. After calving, the animals underwent a series of four cycles of re-synchronization protocols. The season did not affect pregnancy rates when the results of the two treatments were pooled together with regard to the first synchronization protocol, followed by AI. Pregnancy rates were similar during the low breeding season (50.3% vs. 57.4% in OV and P4, respectively), but different during the high breeding season (50.4% vs. 67.7% in OV and P4, respectively; p = 0.000). Logistic regression confirmed a significant effect of treatment and season interaction on pregnancy (p = 0.003). Following re-synchronization, a treatment by season interaction was detected during the low breeding season (odds ratio = 2.233), in favor of P4. Finally, a survival analysis showed a better response of animals subjected to P4 treatment from the second AI onward. In conclusion, the pooled data of pregnancy rates from both treatments between seasons are not different following AIs. Better results, though, were obtained from the implementation of P4 treatment, and are recorded in a season-fashioned mode when the comparison is made following first or cumulative AIs.

Endoscopic and Surgical Removal of Gastrointestinal Foreign Bodies in Dogs: An Analysis of 72 Cases.

In emergency veterinary practice, gastrointestinal foreign body (GFB) removal is a common procedure that is performed with different techniques, such as endoscopy or surgery. The aims of this retrospective, multicentre, clinical study were to report the common locations and types of objects recovered and to investigate clinical factors and outcomes in dogs after surgical or endoscopic treatment for GFB removal. Records of dogs with a GFB diagnosis referred to the Teaching Veterinary Hospital or treated in three different veterinary hospitals from September 2017 to September 2019 were examined. The data obtained from each case included breed, age, clinical signs at presentation, duration of clinical signs, type and location of the GFB, treatment, length of hospitalisation and outcome. Seventy-two dogs were enrolled in the study. There were 42 males (58%) and 30 females (42%). The median age was 36 months (range: 3 months to 8 years). Endoscopic retrieval was performed in 56% of GFBs (located in the stomach or duodenum), whereas 44% of dogs underwent surgery. The type of FB detected varied greatly: kid toy (14%), metallic object/coin (13%), cloth (13%), sock (8%), ball (8%), plastic material (8%), peach stone (7%), fishhook (6%), sewing needle (4%), hair tie (4%), pacifier (3%), plant materials (3%) and others (9%). Moreover, the FBs were classified as sharp (13%, n = 9), pointed (33%, n = 24), blunt (26%, n = 19), or linear (28%, n = 20). In this study, 68% of FBs were localised in the stomach, 25% in the intestinal tract (50% duodenum, 28% jejunum, and 22% ileum), and 7% in both the stomach and small intestine. The type of GFB was not significantly associated with age, site or breed. There was a significant association between the type of GFB and sex: if the dog was male, there was a 38% probability of ingesting linear GFBs. The dog survival rate was 100% in cases treated by gastric endoscopic or surgical removal, 94% in cases treated with enterotomy and 33% in cases in which enterectomy was necessary. Enterectomy and multiple surgical sites were associated with a poor outcome. The presence of vomiting for more than 24 h was significantly associated with death.

Comparison between Image-Guided Transbronchial Cryobiopsies and Thoracoscopic Lung Biopsies in Canine Cadaver: A Pilot Study.

To date, the only method of sampling lung tissue with a high diagnostic yield is represented by surgical lung biopsies (SLB), which are highly invasive and have a high risk/benefit ratio. In humans, transbronchial lung cryobiopsies (TBLC) have recently been introduced, which are described to be less invasive and able to significantly increase diagnostic confidence in most patients with interstitial lung diseases. The aim of this study was to evaluate the feasibility and diagnostic yield of TBLC compared to SLB in small animals. A total of 21 pulmonary cryobiopsies under fluoroscopic and real-time CT fluoroscopic guidance and 21 video-assisted thoracoscopic surgery (VATS) lung biopsies were collected from three dog cadavers. Upon histological examination, cryobiopsy samples were smaller than VATS biopsies, but were still large enough to reach a specific diagnosis or to allow pattern recognition. Morphological features on TBLC and SLB were concordant in all cases. Cryobiopsy samples showed fewer artifacts and a higher percentage of alveolar tissue than VATS samples. TBLC is a feasible and useful alternative to SLB for lung histopathological examination in dogs. The effectiveness and reduced invasiveness of TBLC compared to SLB could represent many advantages in the diagnosis of diffuse lung diseases in small animals.

Crocin Improves the Quality of Cryopreserved Goat Semen in Different Breeds.

The effect of crocin in the semen extender before cryopreservation was evaluated on sperm parameters of 20 bucks of five different breeds: Garganica (GA), Jonica (JO), Maltese (MA), Mediterranean Red (MR) and Saanen (SA). Semen samples were centrifuged, to remove seminal plasma, divided in two aliquots and diluted with Tris-egg-yolk-based extender, containing 0 (control group) and 1 mM crocin. Crocin concentration was established after a preliminary dose trial. On fresh and frozen-thawed sperm, motility, viability, morphology, membrane integrity, DNA fragmentation and ROS levels were evaluated. The freezing process led to a decrease (p < 0.05) in all the sperm parameters recorded, confirming the deleterious effect of cryopreservation on goat semen. The most interesting result regarding the inclusion of crocin in the extender before cryopreservation was as follows: Crocin significantly improved (p < 0.05) sperm motility in all breeds, except for Mediterranean Red, compared to the control group. Furthermore, 1 mM crocin reduced percentage of spermatozoa with DNA fragmentation with a marked decrement (p < 0.05) in Garganica and Saanen, as compared to the control group. Finally, intracellular ROS decreased (p < 0.01) in the crocin-treated sperm of all breeds, as compared to the control. In conclusion, supplementation of 1 mM crocin in the extender decreased oxidative stress, improving sperm motility and the DNA integrity of frozen-thawed sperm in different breeds.

Geographical information system analysis on road accidents involving wandering dogs in the urban area of Naples.

In this study, the spatial distribution of road accidents involving wandering dogs on urban roads of Naples was assessed using kernel density estimation (KDE). The study included 423 dogs victim of road collisions in the period 2012-2015 collected from the medical records of Interdepartmental Centre of Veterinary Radiology, of Pathological Anatomy Service, of Veterinary Teaching Hospital, "Federico II" University of Naples, and of Veterinary Hospital Attendance of the Local Public Health Unit Napoli1. There were a significant prevalence of young male dogs and the KDE demonstrated the presence of five hotspots in five city neighbourhoods. All areas with the highest KDE were found to be peripheral zones in which wide green areas, uncultivated or cultivated, merged with built areas and crossed by large straight roads with a lot of intersections. Wandering dogs as other animals represent a mounting problem on urban roads in Italy, despite of the effort to reduce these populations. Better knowledge of this phenomenon is important with reference to taking countermeasures and improve road safety. It is also important with reference to One Health and the Decade of Action for Road Safety 2011- 2020 of the United Nations.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-ß-OTX2-SNAIL via PTEN inhibition.

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-ß signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-ß activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-ß/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3.10.1093/brain/awy039_video1awy039media15742053534001.

Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma.

Feline herpesvirus 1 (FHV-1) is a widespread cat pathogen inducing rhinitis, conjunctivitis and corneal ulcers. To alleviate acute FHV-1-induced disease, antiviral agents are used often with antibiotics. But sometimes, these treatments, as well as conventional doses of cytokines have moderate efficacy and/or collateral effects. Herein we have investigated the effects of low dose interleukin (IL)-12 plus interferon (IFN)-gamma, prepared by Sequential Kinetic Activated (SKA), on the treatment of FHV-1 infection. Twenty-five, unvaccinated FHV-1-positive cats were recruited into a prospective, randomized, placebo-controlled, double-blinded clinical trial. Fifteen cats were treated for 6 months with oral low doses of SKA IL-12 plus IFN-gamma and 10 cats were treated with placebo. At 1, 6 and 12 months (follow-up) after the beginning of treatment, clinical assessment, PCR assay and blood count were carried out. At follow-up, in treated group, we observed significant (p<0.05) improvements in clinical signs and PCR became negative in 12/15 cats (80%). In placebo, 10/10 cats were PCR-positive, with improvements (30%) or worsening (70%) in clinical signs. Blood values were normal in both groups. Our results show that the low dose therapy, based on activated solutions of IL-12 plus IFN-gamma, represents a novel approach to treat FHV-1 infection in cats.

Urocortinergic system in the testes of normal and cryptorchid dogs.

Cryptorchidism is the most common disorder of the sexual development in dogs, occurring in 13% of the males. Unilateral cryptorchidism is more frequent than bilateral and the right testis seems to be more frequently affected. Urocortin (UCN) is a corticotrophin-releasing hormone (CRH)-related peptide which was observed to affect several functions in male genital organs. The aim of the present study was to investigate the expression of UCN, and its receptors CRHR1 and CRHR2 by immunohistochemistry, Western blot and real-time RT-PCR in the normal and cryptic testis of the dog. The results showed that UCN, CRHR2 and CRHR1 were expressed in normal and cryptic testes. UCN-immunoreactivity (IR) was distributed in germ cells of the normal and cryptic testis. In the normal testis, CRHR2-IR was found in germ and interstitial Leydig cells. In the cryptic testis CRHR2-IR was distributed in gonocytes and interstitial Leydig cells. CRHR1-IR was distributed in the vessel smooth musculature and peritubular myoid cells. UCN and CRHR2 mRNA expression levels were lower in the cryptic than in normal testes. These results suggest that UCN and its receptors might play a role in regulating the spermatogenesis and hormonal activity of interstitial Leydig cells of the dog testis.

A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction.

Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with both reduced cell motility in various cancers and increased metastatic potential in neuroblastomas, osteosarcomas, and hematological malignances. We previously reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1. Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells. This series of events suggests that the Nm23-H1/h-Prune protein complex regulates cancer progression and that its specific impairment could be a new therapeutic strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of-concept of our hypothesis, we used a xenograft model of prostate cancer to evaluate whether impairment of this complex using CPP results in an anti-tumoral effect. Using a mouse orthotopic model with bioluminescent imaging, we show evidences that CPP reduces prostate cancer metastases formation. In conclusion, CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise for the treatment of prostate cancer.

Malignant pilomatricoma with multiple bone metastases in a dog: Histological and immunohistochemical study.

An eleven year-old mongrel dog was referred with a history of left forelimb lameness and an ulcerated mass on the neck. Histologically, the cutaneous neoplasm revealed cystic lobules composed of basaloid cells with abrupt transition to central keratotic material, containing pycnotic and shadow cells. Approximately 3 months after primary diagnosis, a lesion of the cortical bone on the left humerus was observed using X-ray. Samples obtained from the humerus were processed for histopathological examination and the neoplastic tissue was observed to be similar to the type identified in the neck. Based on these findings, the tumor was diagnosed as a malignant pilomatricoma (MP) with bone metastasis. MP is a rare skin tumor that originates from hair matrix cells. To date, only nine reports have been presented in dogs. In the present study, we discuss the cytological and histological patterns of MP, confirmed by immunohistochemistry using ß catenin antibody.

Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.

Nm23-H1 is one of the most interesting candidate genes for a relevant role in Neuroblastoma pathogenesis. H-Prune is the most characterized Nm23-H1 binding partner, and its overexpression has been shown in different human cancers. Our study focuses on the role of the Nm23-H1/h-Prune protein complex in Neuroblastoma. Using NMR spectroscopy, we performed a conformational analysis of the h-Prune C-terminal to identify the amino acids involved in the interaction with Nm23-H1. We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation. Meta-analysis performed on three Neuroblastoma cohorts showed Nm23-H1 as the gene highly associated to Neuroblastoma aggressiveness. We also identified two other proteins (PTPRA and TRIM22) with expression levels significantly affected by CPP. These data suggest a new avenue for potential clinical application of CPP in Neuroblastoma treatment.

Dipyridamole prevents triple-negative breast-cancer progression.

Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated ß-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the expression of IkBα (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways.

Canine lipomas treated with steroid injections: clinical findings.

Lipomas are common benign tumours of fat cells. In most cases, surgical excision is curative and simple to perform; however, such a procedure requires general anaesthesia and may be associated with delayed wound healing, seroma formation and nerve injury in deep and intramuscular tumours. The objective of this study was to evaluate treatment of subcutaneous, subfascial or intermuscular lipomas using intralesional steroid injections in dogs. Fifteen dogs presenting with lipomas were selected for treatment with ultrasound-guided intralesional injection of triamcinolone acetonide at a dose of 40 mg/mL. Nine subcutaneous and subfascial tumours showed a complete regression. The other lipomas decreased in diameter, achieving, in some cases, remission of discomfort and regression of lameness. Steroid injection was a relatively safe and effective treatment for lipomas in dogs; only six dogs experienced polyuria/polydipsia for about 2 weeks post-treatment.

Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models.

Prostate and breast cancer are major causes of death worldwide, mainly due to patient relapse upon disease recurrence through formation of metastases. Chemokines are small proteins with crucial roles in the immune system, and their regulation is finely tuned in early inflammatory responses. They are key molecules during inflammatory processes, and many studies are focusing on their regulatory functions in tumor growth and angiogenesis during metastatic cell seeding and spreading. Bindarit is an anti-inflammatory indazolic derivative that can inhibit the synthesis of MCP-1/CCL2, with a potential inhibitory function in tumor progression and metastasis formation. We show here that in vitro, bindarit can modulate cancer-cell proliferation and migration, mainly through negative regulation of TGF-ß and AKT signaling, and it can impair the NF-κB signaling pathway through enhancing the expression of the NF-κB inhibitor IkB-α. In vivo administration of bindarit results in impaired metastatic disease in prostate cancer xenograft mice (PC-3M-Luc2 cells injected intra-cardially) and impairment of local tumorigenesis in syngeneic Balb/c mice injected under the mammary gland with murine breast cancer cells (4T1-Luc cells). In addition, bindarit treatment significantly decreases the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in 4T1-Luc primary tumors. Overall, our data indicate that bindarit is a good candidate for new therapies against prostate and breast tumorigenesis, with an action through impairment of inflammatory cell responses during formation of the tumor-stroma niche microenvironment.

The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma.

Through microarray analyses, we identified the Mpped2 gene as differentially expressed in two neuroblastoma cell lines induced to differentiation with all-trans retinoic acid. Mpped2 codes for a new metallophosphodiesterase protein, the expression of which inhibits cell proliferation and soft agar colony formation in SH -SY5Y cells. This inhibition is concomitant to an increased proportion of the cells in G0/G1 phase and enhanced caspase 3 activation, effects not seen for the other phosphodiesterases. A Mpped2-null mutation (H67R) abrogates these functions, which indicates that the biochemical activity of Mpped2 is advantageous for cancer suppression. Expression analyses in the "Los Angeles" and "Essen" neuroblastoma gene-array data sets show that increased expression of Mpped2 is associated with good patient prognosis according to Kaplan-Meier analyses. Tumorigenic assays in mice show that overexpression of Mpped2 improves survival rate, substantially impairs tumor growth and induces neuronal differentiation. Altogether, these data show that Mpped2 expression impairs neuroblastoma tumorigenesis, and they establish a basis for future therapeutic applications.