Publications by authors named "Nicola Zizzo"

40 Publications

CT Findings and Histological Evaluation of Red Foxes () with Chronic Head Trauma Injury: A Retrospective Study.

Animals (Basel) 2021 Apr 3;11(4). Epub 2021 Apr 3.

Dipartimento di Medicina Veterinaria, Sez, Patologia Aviare, Università Degli Studi di Bari, Strada Provinciale Per Casamassima Km.3, 70010 Valenzano, Italy.

Large numbers of wild animals are injured every year in road traffic accidents. Scant data are available for rescued wild carnivores, in particular for red foxes. Cases of foxes with head trauma were retrospectively considered for inclusion in this study. Clinical examination, modified Glasgow coma scale (MGCS), computed tomography (CT) examination, therapy, outcome, and post mortem findings of the brain were investigated. In all foxes, cranial vaults lesion occurred in single (67%) or multiple sites (33%). Midline shift and hydrocephalus were observed in this population. The mean survival was 290 (±176) days. In our study, we performed CT scans on average 260 days after fox rescue, and we speculate that persisting clinical signs could be attributed to TBI. In our study, only two foxes were alive at the time of writing. Other foxes were euthanized due to the severity of the clinical signs. CT scans help diagnose chronic lesions and their effect on prognostic judgment for animals released to wildlife environments.
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http://dx.doi.org/10.3390/ani11041010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065572PMC
April 2021

Swine Small Intestine Sealing Performed by Different Vessel Sealing Devices: Ex-Vivo Test.

Vet Sci 2021 Feb 22;8(2). Epub 2021 Feb 22.

Dipartimento dell'Emergenze e Trapianti di Organi (D.E.T.O.), Sezione di Cliniche Veterinarie e Produzioni Animali, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy.

This study aimed to evaluate the sealing quality of swine small intestine using different laparoscopic radiofrequency vessel sealing devices (two 5 mm: RFVS-1 and -2; one 10 mm: RFVS-3) and a harmonic scalpel (HS) compared to golden standard closure technique. The study was divided into two arms. In study arm 1: n = 50 swine intestinal loops (10 per group) were transected with each instrument and the loops in which the devices provided complete sealing, at the gross inspection, were tested for maximum burst pressure (BP) and histological evaluation and compared to an automatic linear stapler. After the BP tests, the devices that achieved significantly lower BP values were excluded from the second arm. The RFVS-1 and -3 provided statistically significant results and were used in study arm 2, to obtain full-thickness biopsies along the antimesenteric border of the loop and were compared with hand-sewn intestinal closure (n = 30; 10 per group). The biopsies were histologically evaluated for thermal injury and diagnostic features, and intestinal loops tested for BP. RFVS-3 achieved comparable results (69.78 ± 4.23 mmHg, interquartile range (IQR) 5.8) to stapler closing technique (71.09 ± 4.22 mmHg, IQR 4.38; > 0.05), while the RFVS-1 resulted in significantly ( < 0.05) lower BP (45.28 ± 15.23 mmHg, IQR 24.95) but over the physiological range, conversely to RFVS-2 (20.16 ± 7.19 mmHg, IQR 12.02) and HS (not measurable). RFVS-3 resulted not significantly different ( > 0.05) (45.09 ± 8.75 mmHg, IQR 10.48) than Suture (35.71 ± 17.51 mmHg, IQR 23.77); RFVS-1 resulted significantly lower values (23.96 ± 10.63 mmHg, IQR 9.62; < 0.05). All biopsies were judged diagnostic. Data confirmed that RFVS-1 and -3 devices provided suitable intestinal sealing, with BP pressures over the physiological range. Conversely, the HS and RFVS-2 should not be considered for intestinal sealing. RFVS devices could be employed to obtain small intestine stump closure or full-thickness biopsies. However, further studies should be performed in live animals to assess the role of the healing process.
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http://dx.doi.org/10.3390/vetsci8020034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926574PMC
February 2021

Mast Cells Positive for c-Kit Receptor and Tryptase Correlate with Angiogenesis in Cancerous and Adjacent Normal Pancreatic Tissue.

Cells 2021 Feb 19;10(2). Epub 2021 Feb 19.

Interventional Oncology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy.

Background: Mast cells (MCs) contain proangiogenic factors, in particular tryptase, associated with increased angiogenesis in several tumours. With special reference to pancreatic cancer, few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue (PDAT) and adjacent normal tissue (ANT). In this study, density of mast cells positive for c-Kit receptor (MCDP-c-KitR), density of mast cells positive for tryptase (MCDPT), area of mast cells positive for tryptase (MCAPT), and angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated in a total of 45 PDAT patients with stage TNM.

Results: For each analysed tissue parameter, the mean ± standard deviation was evaluated in both PDAT and ANT and differences were evaluated by Student's -test ( ranged from 0.001 to 0.005). Each analysed tissue parameter was then correlated to each other one by Pearson -test analysis ( ranged from 0.01 to 0.03). No other correlation among MCDP-c-KitR, MCDPT, MCAPT, MVD, EA and the main clinical-pathological characteristics was found.

Conclusions: Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy.
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http://dx.doi.org/10.3390/cells10020444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923170PMC
February 2021

Microvascular Density, Endothelial Area, and Ki-67 Proliferative Index Correlate Each Other in Cat Post-Injection Fibrosarcoma.

Cells 2020 12 28;10(1). Epub 2020 Dec 28.

Department of Veterinary Medicine, Section of Veterinary Pathology and Comparative Oncology, University of Bari "Aldo Moro", Strada p.le per Casamassima, km 3, 70010 Valenzano, Bari, Italy.

Soft tissue sarcomas are a large group of different tumor types both in humans and in animals. Among them, fibrosarcoma is the most frequent malignant mesenchymal tumoral form in cats, representing up to 28% of all cat skin tumors, while human fibrosarcoma, fortunately, only represents 5% of all sarcomas and 0.025% of the world-wide burden of tumors. This low incidence in humans leads to consideration of this group of tumoral diseases as rare, so therapeutic options are few due to the difficulty of starting clinical trials. In this context, the identification of research models for fibrosarcomas could be of great interest to deepen knowledge in this field and recognize new or possible biological pathways involved in tumor progression and metastasis. Angiogenesis is considered a fundamental scattering cause of tumor aggressiveness and progression in all forms of cancer, but only a few research parameters were developed and reported to express them quantitatively and qualitatively. The role in angiogenesis of microenvironmental stromal cells, such as fibroblasts, lymphocytes, mast cells, and macrophages, was largely demonstrated since this topic was first approached, while quantification of new vessels and their blood capacity in tumoral area is a relatively recent approach that could be well developed thanks to expertise in immunohistochemistry and image analysis. In this paper, a crossing study evaluating microvascular density (MVD), endothelial area (EA), and Ki-67 proliferative index was reported for a series of formalin-fixed and paraffin-embedded tissue samples from 99 cat patients, affected by cat post-injection fibrosarcoma, by using a till ×400 magnification light microscopy. We aim to demonstrate that cat pets may be considered a useful animal model for better studying the correspondent human diseases and we report, for the first time to our knowledge, experimental data in terms of correlation among MVD, EA, and Ki-67 strictly involved in aggressiveness and tumoral progression.
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http://dx.doi.org/10.3390/cells10010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823643PMC
December 2020

Pathophysiological Consequences of KATP Channel Overactivity and Pharmacological Response to Glibenclamide in Skeletal Muscle of a Murine Model of Cantù Syndrome.

Front Pharmacol 2020 30;11:604885. Epub 2020 Nov 30.

Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari "Aldo Moro", Bari, Italy.

Cantù syndrome (CS) arises from mutations in and genes that lead to gain of function (GOF) of ATP-sensitive potassium (KATP) channels containing SUR2A and Kir6.1 subunits, respectively, of KATP channels. Pathological consequences of CS have been reported for cardiac and smooth muscle cells but consequences in skeletal muscle are unknown. Children with CS show muscle hypotonia and adult manifest fatigability. We analyzed muscle properties of Kir6.1[V65M] CS mice, by measurements of forelimb strength and ultrasonography of hind-limb muscles, as well as assessing KATP channel properties in native (FDB) and (SOL) fibers by the patch-clamp technique in parallel with histopathological, immunohistochemical and Polymerase Chain Reaction (PCR) analysis. Forelimb strength was lower in Kir6.1 mice than in WT mice. Also, a significant enhancement of echodensity was observed in hind-limb muscles of Kir6.1 mice relative to WT, suggesting the presence of fibrous tissue. There was a higher KATP channel current amplitude in Kir6.1 FDB fibers relative to WT and a reduced response to glibenclamide. The IC of glibenclamide to block KATP channels in FDB fibers was 1.3 ± 0.2 × 10 M in WT and 1.2 ± 0.1 × 10 M in Kir6.1 mice, respectively; and it was 1.2 ± 0.4 × 10 M in SOL WT fibers but not measurable in Kir6.1 fibers. The sensitivity of the KATP channel to MgATP was not modified in Kir6.1 fibers. Histopathological/immunohistochemical analysis of SOL revealed degeneration plus regressive-necrotic lesions with regeneration, and up-regulation of Atrogin-1, MuRF1, and BNIP3 mRNA/proteins in Kir6.1 mice. Kir6.1 mutation in skeletal muscle leads to changes of the KATP channel response to glibenclamide in FDB and SOL fibers, and it is associated with histopathological and gene expression changes in slow-twitch muscle, suggesting marked atrophy and autophagy.
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http://dx.doi.org/10.3389/fphar.2020.604885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734337PMC
November 2020

Absorbable fixation straps for laparoscopic gastropexy in dogs.

Vet Surg 2020 Nov 11. Epub 2020 Nov 11.

Dipartimento Dell'Emergenze e trapianti di Organo, sez Cliniche Veterinarie e PA, Università degli studi di Bari, Valenzano, Bari, Italy.

Objective: To evaluate the feasibility and efficacy of laparoscopic absorbable fixation straps (AFS) for laparoscopic gastropexy in dogs.

Study Design: Cadaveric and prospective clinical study.

Animals: Five dog cadavers for the cadaveric study; 12 dogs for the clinical study.

Methods: The pyloric antrum was affixed to the abdominal wall laparoscopically by applying a series of straps. The cadaveric study assessed potential challenges during the procedure and stomach mucosal penetration. For the clinical study, the total duration of surgery, time to complete the gastropexy, and the number of straps used were recorded. Ultrasound evidence of adhesion, complications, and weight were monitored at 7, 30, and 90 days after surgery. Owner satisfaction was evaluated at the 6-month follow-up.

Results: The total duration of surgery was 25.8 minutes (range, 19-39; SD, 6.7), and the time to complete the gastropexy was 10.1 minutes (range, 7-19; SD, 3.9). The linear regression analysis revealed an inverse correlation between the time to complete the gastropexy and the order of the surgeries (r = 0.75, P < .05). No complications were recorded. Ultrasound examination was used to confirm gastropexy at all follow-ups.

Conclusion: Laparoscopic gastropexy with AFS was performed in both cadavers and clinical animals with minimal complications. Persistent adhesion was demonstrated during ultrasound evaluations and in one postmortem evaluation.

Clinical Significance: This novel laparoscopic technique can be employed safely, effectively, and reasonably quickly, and the learning curve is expected to be relatively short.
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http://dx.doi.org/10.1111/vsu.13543DOI Listing
November 2020

Systematic Pathologic Findings Report of (Horsfield, 1823) (Rodentia, Sciuridae) Squirrels from Maratea area (South Italy) to Investigate Species-Specific Pathologies, Reliability of CO Euthanasia Method, and Possible Use as Environmental Sentinels.

Animals (Basel) 2020 Sep 30;10(10). Epub 2020 Sep 30.

Department of Veterinary Medicine, University of Bari "Aldo Moro", Strada Prov.le per Casamassima Km. 3 70010 Valenzano (Bari), Italy.

The aim of the present study was to macroscopically and microscopically describe the main pathological findings occurring in this invasive species, in order to better understand the real risks for naïve animals and humans. The present study was conducted on squirrels (n = 165), captured in the Maratea area and euthanatized with CO according to a population control of invasive species of the Italian Agriculture Ministry project (ex CIPE project) and conferred to the Department of Veterinary Medicine of Bari (Italy). Macroscopic analysis demonstrated heart, lung, and liver congestion, probably due to the euthanasia method, and variable lesions of bowel, liver, and kidney. The microscopically examination showed the presence of lymphocytic infiltration in the lower layers of the bowel, suggesting enteritis. To the best of our knowledge, this is the first systemic report of gross and microscopical anatomopathological lesions in in South Italy. The results could be useful to fill a gap of knowledge of this species in Italy.
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http://dx.doi.org/10.3390/ani10101771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600486PMC
September 2020

Evaluation of the Occurrence of False Aneurysms During Halal Slaughtering and Consequences on the Animal's State of Consciousness.

Animals (Basel) 2020 Jul 13;10(7). Epub 2020 Jul 13.

Interdisciplinary Department of Medicine, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.

This study evaluated the occurrence of false aneurysms and reflexes in bovines, associated with the point along the neck where the cut was performed. The survey was carried out on a total of 1200 male beef cattle, belonging mainly to the Charolais and Limousin breeds, aged between twelve and twenty-four months. In the slaughterhouse, three operators, identified by convention as Operator C4, Operator C2, and Operator C1, performed the Halal slaughtering. Each operator carried out the slaughter of 400 animals and, on the basis of his own professional training, performed the cutting of the vessels at different points along the neck: Operator C4 between the third and fourth cervical vertebrae; Operator C2 at the level of the second cervical vertebra; and Operator C1 at the first cervical vertebra. The occurrence of false aneurysms was assessed on the basis of the different cutting site used by the three operators. Then, the evaluation of consciousness indicators, that is, rhythmic breathing and eye response, closely related to a slow bleeding process and to a delayed loss of brain function, was carried out 90 s post-bleeding. The group of cattle slaughtered by Operator C4 had a prevalence of false aneurysms of 10.25%. Conversely, the other two groups of cattle slaughtered by Operators C2 and C1 showed false aneurysm formation in 7.25% of each case. Further, 37.5% of the animals (18 for Operator C4, 17 for Operator C2, and 16 for Operator C1) with signs of consciousness 90 s after sticking were consequent to the onset of false aneurysms and, more precisely, they were owing to a late second cut of the vessel carried out by the operator, when false aneurysms occurred. The results of the research showed that the cutting point chosen by the operator is a key element in determining the onset of false aneurysms.
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http://dx.doi.org/10.3390/ani10071183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401542PMC
July 2020

The hydroxypropyl-β-cyclodextrin-minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia.

Pharmacol Res Perspect 2020 06;8(3):e00585

Section of Pharmacology, Department of Pharmacy - Pharmaceutical Sciences, University of Bari, Bari, Italy.

The efficacy of minoxidil (MXD) ethanolic solutions (1%-5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%-3.5% w/v) and of single and twice daily doses (3.5% w/v) of a novel hydroxypropyl-β-cyclodextrin MXD GEL formulation (MXD/HP-β-CD) and a MXD solution were investigated in male rats. The cardiovascular effects were evaluated by telemetric monitoring of ECG and arterial pressure in free-moving rats. Ultrasonographic evaluation of cardiac morphology and function, and histopathological and biochemical analysis of the tissues, were performed. A pharmacovigilance investigation was undertaken using the EudraVigilance database for the evaluation of the potential cancer-related effects of topical MXD. Following the application of repeated escalating doses of MXD solution, cardiac hypertrophy, hypotension, enhanced serum natriuretic peptides and K -ion levels, serum liver biomarkers, and histological lesions including renal cancer were observed. In addition, the administration of a twice daily dose of MXD solution, at SF rat vs human = 311, caused reductions in the systolic, diastolic, and mean blood pressure of the rats (-30.76 ± 3%, -28.84 ± 4%, and -30.66 ± 5%, respectively, vs the baseline; t test P < .05). These effects were not reversible following washout of the MXD solution. Retrospective investigation showed 32 cases of cancer associated with the use of topical MXD in humans. The rats treated with MXD HP-β-CD were less severely affected. MXD causes proliferative adverse effects. The MXD HP-β-CD inclusion complex reduces these adverse effects.
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http://dx.doi.org/10.1002/prp2.585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203570PMC
June 2020

Histological features of Rickettsia-like organisms in the European flat oyster (Ostrea edulis L.).

Environ Sci Pollut Res Int 2020 Jan 9;27(1):882-889. Epub 2019 Dec 9.

Department of Veterinary Medicine, Veterinary Pathology and Comparative Oncology Unit, University of Bari Aldo Moro, Valenzano, 70010, Bari, Italy.

The European flat oyster (Ostrea edulis L.) represents an economically important oyster production in Southern Italy, widespread in natural beds along the coast. The practice to be eaten raw is an everlasting concern for possible health risk with a need to stringently monitor the health of aquatic environment. A screening survey using histopathological examination was undertaken by harvesting O. edulis from different sites along the Apulian coast of Italy. Tissue samples of the digestive gland, kidney, gonad, and gill were provided for morphologic study in light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) analysis. The LM observations revealed spherical cytoplasmic inclusions as basophilic prokaryote colonies in 13/250 oysters. The TEM and SEM confirmed the presence of intracytoplasmic inclusions of Rickettsia-like organisms (RLOs), merely in the epithelial cells of the digestive gland tubule tissues in the 13 oysters. Within intracytoplasmic vacuoles, RLOs exhibited a prokaryotic characteristic ultrastructure with transverse binary fission, a DNA zone full of chromatin fibers and a granular periplasmic ribosome zone. O. edulis were found positive for RLOs in wild oysters from Manfredonia, while the other sites were found free of pathological inclusions. Thus, we present the first report of a Rickettsia-like infection in the Apulian wild oyster (O. edulis) from Italy, including an ultrastructural description and pathological characterization.
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http://dx.doi.org/10.1007/s11356-019-07007-8DOI Listing
January 2020

Thymidine Phosphorylase Expression and Microvascular Density Correlation Analysis in Canine Mammary Tumor: Possible Prognostic Factor in Breast Cancer.

Front Vet Sci 2019 25;6:368. Epub 2019 Oct 25.

Interventional and Medical Oncology Unit, Department of Pathology National Cancer Research Centre, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy.

The thymidine phosphorylase (TP) is a key enzyme involved in the metabolism of pyrimidines. Inhibition or downregulation of this enzyme causes accumulation of metabolites with consequences in DNA replication. TP regulates angiogenesis and chemotactic activity of endothelial cells. Different studies showed the presence of TP upregulation in human cancer but the correlation between TP expression and the microvascular density (MVD) in canine mammary tumors is unknown. The aim of this study was to investigate a possible correlation between the MVD and TP expression in tumor cells of canine mammary tumors of different degree of severity (G1-G3) by immunohistochemical analysis. Sixty-eight samples of spontaneous mammary neoplasia of 5-12 cm in diameter were collected from purebred and mixed-breed dogs (mean aged = 9.5 ± 7), not subject to chemotherapy treatments in veterinary clinics. Histopathological analysis and immunostaining were performed. Carcinoma simple samples have been classified as 72.06% of tubule-papillary, 20.59% cysto-papillary, and 7.35% tubular carcinomas. Immunostainings revealed a marked cytoplasmic expression of TP in 30.88% of samples, mild in 32.35%, weaker in 22.07%, and negative in 14.70%. The correlation analysis and two-way ANOVA showed a linear correlation between MVD and TP with a coefficient of correlation () > 0.5 ( < 0.05) in G2 and G3. No correlation between variables was found in G1. These findings suggest that cytoplasmic TP overexpression is correlated with microvascular density in canine mammary tumors, in severe grade, and it can be a potential prognostic factor in breast cancer.
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http://dx.doi.org/10.3389/fvets.2019.00368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823610PMC
October 2019

. in Loggerhead Sea Turtles (): From Colonization to Infection.

Vet Pathol 2020 01 29;57(1):139-146. Epub 2019 Oct 29.

Wageningen University &Research, BU Biointeractions and Plant Health, Wageningen, the Netherlands.

With the aim of evaluating the presence of . in sea turtles with and without lesions and assessing the risk factors favoring colonization and/or infection, 74 loggerhead sea turtles () admitted to rescue and rehabilitation clinics in Italy were analyzed. The study compared 31 individuals with no apparent macroscopic lesions and 43 individuals with macroscopic lesions. Shell and skin samples were analyzed using Calcofluor white with 10% potassium hydroxide, standard histopathological examination, and fungal cultures. . were isolated more frequently from animals with superficial lesions (39%) than from those with no macroscopic lesions (16%). Isolates from animals with superficial lesions were species complex (FSSC) lineages haplotypes 9, 12, and 27 (unnamed lineages), FSSC-2 (), (27%), and (3%). In contrast, only haplotypes 9 and 12 were isolated from animals with no macroscopic lesions. The presence of lesions was identified as a risk factor for the occurrence of . Of the 74 animals, only 7 (9.5%) scored positive on microscopic examination with Calcofluor, and histological examination of those 7 animals revealed necrosis, inflammatory cells, and fungal hyphae in the carapace and skin. The results of this study suggest that fusariosis should be included in the differential diagnosis of shell and skin lesions in sea turtles. Direct examination using Calcofluor and potassium hydroxide was not useful to diagnose the infection. Histopathological examination and fungal culture should be performed to ensure correct treatment and infection control.
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http://dx.doi.org/10.1177/0300985819880347DOI Listing
January 2020

Neurological symptoms and mortality associated with Streptococcus gallolyticus subsp. pasteurianus in calves.

Vet Microbiol 2019 Sep 23;236:108369. Epub 2019 Jul 23.

Department of Veterinary Medicine, University of Bari "Aldo Moro", Str. Prov. per Casamassima Km 3, 70010, Valenzano, BA, Italy.

Suppurative meningitis-meningoencephalitis (M-ME) is a sporadic disease in neonatal ungulates and only a few studies have reported the involvement of Streptococcus bovis/Streptococcus equinus complex (SBSEC) members in bovine neonatal M-ME. The SBSEC taxonomy was recent revised and previous biotype II/2 was reclassified as S. gallolyticus subsp. pasteurianus (SGP). The aim of this study was to describe a case of fatal neonatal neurological syndrome associated with SGP in calves. Ten calves were monitored because of neurological hyperacute symptoms associate with bilateral hypopyon and death. They were not fed with maternal colostrum; two of them died and were subjected to bacteriological, histopathological and biomolecular analysis as well as antibiotic susceptibility test. Both animals presented lesions mostly concentrated to meninges and brain and had bilateral hypopyon. Nine strains isolated in purity from brain, ocular humors and colon were identified as S. bovis group by using the API Strep system and as S. gallolyticus by using the 16S rRNA sequence. Two of these strains where subjected to WGS analysis that confirmed the sub-species identification and the clonality of the two SGP strains. The strains were found resistant to OT, SXT, MTZ and EN and susceptible to AMP, AMC, KZ and CN. We hypothesized that the syndrome observed could be due to the lack of maternal colostrum feeding. A timely and precise diagnosis could have likely prevented the death of the calves and, since the zoonotic potential of SBSECs members is known, accurate and rapid identification is required.
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http://dx.doi.org/10.1016/j.vetmic.2019.07.021DOI Listing
September 2019

Sarcocystis bertrami in skeletal muscles of donkeys (Equus africanus asinus) from Southern Italy.

Vet Parasitol Reg Stud Reports 2019 04 14;16:100283. Epub 2019 Mar 14.

Department of Veterinary Medicine, University of Bari "Aldo Moro", Valenzano, Italy.

Among the protozoa of the genus Sarcocystis (Apicomplexa; Sarcocystidae), Sarcocystis bertrami (syn. Sarcocystis fayeri) is an obligate intracellular parasite of donkeys and horses with worldwide distribution. Here, we report the detection of S. bertrami in naturally infected donkeys from southern Italy and describe their structure by light microscopy (LM) and transmission electron microscopy (TEM). Protozoal cysts were detected both morphologically and molecularly in skeletal muscles of 28.57% (40/140) donkeys. Mature cysts of S. bertrami were found in skeletal muscle measuring 31-102 μm long and 19-83 μm wide with radially striated thick cyst wall. The high prevalence of infected donkeys suggests that dogs, the definitive hosts of S. bertrami, are contaminating environment with environmentally resistant sporocysts. Considering the increased consumption of raw donkey meat results also suggest a potential risk for human health.
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http://dx.doi.org/10.1016/j.vprsr.2019.100283DOI Listing
April 2019

Cell Cycle Regulation by Ca-Activated K⁺ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells.

Int J Mol Sci 2018 Aug 18;19(8). Epub 2018 Aug 18.

Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, 70125 Bari, Italy.

The effects of Ca-activated K⁺ (BK) channel modulation by Paxilline (PAX) (10⁻10 M), Iberiotoxin (IbTX) (0.1⁻1 × 10 M) and Resveratrol (RESV) (1⁻2 × 10 M) on cell cycle and proliferation, AKT1p phosphorylation, cell diameter, and BK currents were investigated in SH-SY5Y cells using Operetta-high-content-Imaging-System, ELISA-assay, impedentiometric counting method and patch-clamp technique, respectively. IbTX (4 × 10 M), PAX (5 × 10 M) and RESV (10 M) caused a maximal decrease of the outward K⁺ current at +30 mV (Vm) of -38.3 ± 10%, -31.9 ± 9% and -43 ± 8%, respectively, which was not reversible following washout and cell depolarization. After 6h of incubation, the drugs concentration dependently reduced proliferation. A maximal reduction of cell proliferation, respectively of -60 ± 8% for RESV (2 × 10 M) (IC50 = 1.50 × 10 M), -65 ± 6% for IbTX (10 M) (IC50 = 5 × 10 M), -97 ± 6% for PAX (1 × 10 M) (IC50 = 1.06 × 10 M) and AKT1p dephosphorylation was observed. PAX induced a G1/G2 accumulation and contraction of the S-phase, reducing the nuclear area and cell diameter. IbTX induced G1 contraction and G2 accumulation reducing diameter. RESV induced G2 accumulation and S contraction reducing diameter. These drugs share common actions leading to a block of the surface membrane BK channels with cell depolarization and calcium influx, AKT1p dephosphorylation by calcium-dependent phosphatase, accumulation in the G2 phase, and a reduction of diameter and proliferation. In addition, the PAX action against nuclear membrane BK channels potentiates its antiproliferative effects with early apoptosis.
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http://dx.doi.org/10.3390/ijms19082442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121591PMC
August 2018

Heart valve pathology in regularly slaughtered horses.

Vet Ital 2018 06;54(2):165-168

Università degli Studi di Bari

In this study we examined macroscopic and microscopic lesions in the mitral valves of 50 regularly slaughtered horses in Italy. Macroscopically the results were minor. Microscopic lesions to the valve were found in both young and elderly subjects, confirming that there is no correlation between age and onset of lesions. We set out to evaluate whether the lesions correspond to valve disorder during the life of the animal.
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http://dx.doi.org/10.12834/VetIt.1394.7616.1DOI Listing
June 2018

C-Kit receptor and tryptase expressing mast cells correlate with angiogenesis in breast cancer patients.

Oncotarget 2018 Jan 22;9(8):7918-7927. Epub 2017 Dec 22.

Interventional and Medical Oncology Unit, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy.

C-Kit protein is a transmembrane tyrosine kinase (TK) receptor (c-KitR-TK), which is predominantly expressed on mast cells (MCs) playing a role in tumor angiogenesis. It could be also expressed on epithelial breast cancer cells (EBCCs), but no data have been published regarding the correlation between mast cells positive to c-KitR (MCs-c-KitR), EBCCs positive to c-KitR (EBCCs-c-KitR), BC angiogenesis in terms of microvessel density (MVD) and the main clinic-pathological features. This study aims to evaluate the above parameters and their correlations in a series of selected 121 female early BC patients. It has been found a strong correlation between MVD and MCDPT, and MCs-c-KitR, MVD and MCs density positive to tryptase (MCDPT), and MCs-c-KitR and MCDPT by Pearson correlation. These data suggest an involvement of both MCDPT and MCs-c-KitR in BC tumor angiogenesis. Furthermore, BC tissue expressing c-KitR could be a putative predictive factor to c-KitR-TK inhibitors. In this way, selected patients with higher MCs-c-KitR could be candidate to receive c-KitR-TK inhibitors (e.g. masitinib, sunitinib) or tryptase inhibitors (e.g. nafamostat mesilate, gabexate mesilate).
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http://dx.doi.org/10.18632/oncotarget.23722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814269PMC
January 2018

Characterization of minoxidil/hydroxypropyl-β-cyclodextrin inclusion complex in aqueous alginate gel useful for alopecia management: Efficacy evaluation in male rat.

Eur J Pharm Biopharm 2018 Jan 24;122:146-157. Epub 2017 Oct 24.

Pharmaceutical Technology, Department of Pharmacy - Pharmaceutical Sciences, University of Bari, Italy.

Solid inclusion complex between hydroxypropyl-β-cyclodextrin (HP-β-CD) and minoxidil (MXD) was prepared by freeze-drying and characterized by yield, drug loading and dissolution rate. Moreover, the complex was formulated as alginate gel (GEL HP-β-CD)/MXD 3.5% w/w). The efficacy of the novel GEL HP-β-CD)/MXD 3.5% w/w and of MXD 3.5% w/w ethanolic/propylene-glycol solution (MXD solution) were evaluated by monitoring the hair growth of dorsal skin 1-4 weeks after depilation followed by histological analysis and gene expression in skin biopsies in male rat. Patch-clamp experiments and cell-dehydrogenase activity (CDA) were performed to evaluate the capability of the formulations to activate "in vitro" the ATP-sensitive K-channels (KATP) and their effects on cell viability in skin fibroblasts. After 3 weeks, the MXD solution and MXD/HP-β-CD GEL enhanced the hair growth, respectively, of 80.1 ± 2% and 84.3 ± 4% vs controls. After 4 weeks, the MXD/HP-β-CD GEL significantly enhanced the hair length and bulb diameter vs others groups. The MXD/HP-β-CD GEL significantly enhanced the mRNA levels of the SUR2 and Kir6.1 subunits of the KATP channels and AKT2 vs other groups. The AR gene was down-regulated vs controls following the treatment with either MXD formulations. Either MXD (10 M) formulations were effective in potentiating the KATP currents. The MXD solution and its vehicle after 9 h of incubation time, but not MXD/HP-β-CD, reduced CDA in fibroblasts. In sum, the MXD/HP-β-CD GEL shows a favorable profile following topical long-term use.
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http://dx.doi.org/10.1016/j.ejpb.2017.10.015DOI Listing
January 2018

The density of mast cells c-Kit and tryptase correlates with each other and with angiogenesis in pancreatic cancer patients.

Oncotarget 2017 Sep 31;8(41):70463-70471. Epub 2017 Jul 31.

Interventional Radiology Unit with Integrated Section of Traslational Medical Oncology, National Cancer Research Centre, "Giovanni Paolo II", Bari, Italy.

Literature data suggest that inflammatory cells such as mast cells (MCs) are involved in angiogenesis. MCs can stimulate angiogenesis by releasing of well identified pro-angiogenic cytokines stored in their cytoplasm. In particular, MCs can release tryptase, a potent and pro-angiogenic factor. Nevertheless, few data are available concerning the role of MCs positive to tryptase in primary pancreatic cancer angiogenesis. This study analyzed the correlation between mast cells positive to c-Kit receptor (c-Kit MCs), the density of MCs expressing tryptase (MCD-T) and microvascular density (MVD) in primary tumor tissue from patients affected by pancreatic ductal adenocarcinoma (PDAC). A series of 35 PDAC patients with stage TNM (by AJCC for Pancreas Cancer Staging 7 Edition) were selected and then undergone to surgery. Tumor tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of number of c-Kit MCs, MCD-T and MVD. The above parameters were related each other and with the most important main clinico-pathological features. A significant correlation between c-Kit MCs, MCD-T and MVD groups each other was found by Pearson t-test analysis (r ranged from 0.75 to 0.87; p-value ranged from 0.01 to 0.04). No other significant correlation was found. Our preliminary data, suggest that tumor microenvironmental MCs evaluated in terms of c-Kit MCs and MCD-T may play a role in PDAC angiogenesis and they could be further evaluated as a novel tumor biomarker and as a target of anti-angiogenic therapy.
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http://dx.doi.org/10.18632/oncotarget.19716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642569PMC
September 2017

First report of Angiostrongylus vasorum in a wild red fox (Vulpes vulpes) from Apulia (Italy).

Vet Ital 2017 09 5;53(3):259-262. Epub 2017 Apr 5.

University of Bari, Department of Veterinary Medicine, 70010 Valenzano (BA), Italy.

Severe lung strongylosis was detected in a wild red fox (Vulpes vulpes) (1/12) from Apulia (Italy). We performed routine diagnostics on 12 foxes found dead in Apulia. Eleven of them showed lesions consistent with a vehicle collision. However, the remaining fox appeared to have died from other causes. At necropsy we observed, catarrhal enteritis, fatty liver, lung congestion with some areas rm in consistence and brain haemorrhages and malacia. Histopathology revealed lung brosis with mononucleate cells in ltration, thrombosis a several larval nematodes spread in the parenchyma, interstitial nephritis, interstitial myocarditis, encephalitis, encephalomalacia, and a brain granuloma. The larvae recovered from the lung parenchyma were identi ed as the rst stage larvae of Angiostrongylus vasorum. This is the rst documented report of angiostrongylosis in a fox in Southern Italy.
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http://dx.doi.org/10.12834/VetIt.438.2132.3DOI Listing
September 2017

Tryptase mast cell density, protease-activated receptor-2 microvascular density, and classical microvascular density evaluation in gastric cancer patients undergoing surgery: possible translational relevance.

Therap Adv Gastroenterol 2017 Apr 1;10(4):353-360. Epub 2017 Feb 1.

Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, 'Giovanni Paolo II', Bari, Italy.

Background: Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular, MCs can release tryptase, a potent and proangiogenic factor protease-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. Nevertheless, no data are available concerning the relationship among tryptase MC density (TMCD), endothelial cells (ECs) positive to PAR-2 microvascular density (PAR-2-MVD) and classical MVD (C-MVD) in gastric cancer (GC) angiogenesis.

Methods: In this study, we analyzed the correlation of TMCD, PAR-2-MVD, C-MVD with each other and with the main clinicopathological features in GC patients who underwent surgery. A series of 77 GC patients with stage TNM (classified by the American Joint Committee on Cancer for Gastric Cancer, 7th edition) were selected and then underwent surgery.

Results: Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of numbers of TMCD, PAR-2-MVD and C-MVD. A significant correlation between the TMCD, PAR-2-MVD and C-MVD groups with each other was found by Pearson -test analysis ( ranged from 0.64 to 0.76; value ranged from 0.02 to 0.03). There was no other significant correlation between the above parameters and clinicopathological features.

Conclusions: Our preliminary data suggest that TMCD and PAR-2-MVD may play a role in GC angiogenesis and they could be further evaluated as a target of antiangiogenic therapy.
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http://dx.doi.org/10.1177/1756283X16673981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405880PMC
April 2017

Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery.

Int J Mol Sci 2016 Nov 15;17(11). Epub 2016 Nov 15.

Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", viale Orazio Flacco 65, 70124 Bari, Italy.

Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage TNM₀ (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson -test analysis ( ranged from 0.74 to 0.79; -value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies.
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http://dx.doi.org/10.3390/ijms17111905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133903PMC
November 2016

Angiostrongylus chabaudi in felids: New findings and a review of the literature.

Vet Parasitol 2016 Sep 11;228:188-192. Epub 2016 Sep 11.

Department of Veterinary Medicine, Università degli Studi di Bari, Valenzano, Bari, Italy. Electronic address:

Cardiopulmonary infections by Angiostrongylus chabaudi affect domestic and wild felids but, due to limited information on the biology of this nematode, its pathogenicity remains unclear. This article describes the histopathological alterations associated with Angiostrongylus infection in a wildcat from Bulgaria, and reviews current literature on this feline angiostrongylid. Nematodes were isolated from lung lavage and faecal samples of a road killed wildcat in Southern Bulgaria. The morphological identification of parasite larvae as A. chabaudi was confirmed by molecular analysis of part of the 18S ribosomal RNA gene. Upon histopathological examination, severe granulomatous pneumonia, ranging from multifocal to coalescing, and pulmonary vascular lesions were observed. Extensive alveolar collapse, alveolar emphysematous changes, parenchymal haemorrhages and small artery wall hyperplasia were observed in the parenchyma adjacent to the granulomas. Histopathological examination revealed the presence of cross-sections of adult female parasites within the lumen of the pulmonary artery branches, the intima altered markedly by subendothelial proliferation and oedematous changes. This study compliments current knowledge of the pathogenesis of feline angiostrongylosis by A. chabaudi in wildcats, as well as of the distribution of this little-known parasite.
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http://dx.doi.org/10.1016/j.vetpar.2016.09.007DOI Listing
September 2016

Mast cells positive to tryptase, endothelial cells positive to protease-activated receptor-2, and microvascular density correlate among themselves in hepatocellular carcinoma patients who have undergone surgery.

Onco Targets Ther 2016 21;9:4465-71. Epub 2016 Jul 21.

Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, "Giovanni Paolo II"

Background: Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase phosphorylation. Nevertheless, no data are available concerning the relationship between MC density positive to tryptase (MCDPT), endothelial cells positive to PAR-2 forming microvascular density (PAR-2-MVD), and classical MVD (C-MVD) in hepatocellular carcinoma (HCC) angiogenesis. This study analyzed the correlation between MCDPT, PAR-2-MVD, and C-MVD, each correlated to the others and to the main clinicopathological features, in early HCC patients who underwent surgery.

Methods: A series of 53 HCC patients with early stage (stage 0 according to the Barcelona Clinic Liver Cancer Staging Classification) were selected and then underwent surgery. Tumor tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCDPT, PAR-2-MVD, and C-MVD.

Results: A significant correlation between MCDPT, PAR-2-MVD, and C-MVD groups, each correlated to the others, was found by Pearson t-test analysis (r ranged from 0.67 to 0.81; P-value ranged from 0.01 to 0.03). No other significant correlation was found.

Conclusion: Our in vivo pilot data suggest that MCDPT and PAR-2-MVD may play a role in HCC angiogenesis and could be further evaluated as a target of antiangiogenic therapy.
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http://dx.doi.org/10.2147/OTT.S105368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959580PMC
August 2016

ERas protein is overexpressed and binds to the activated platelet-derived growth factor β receptor in bovine urothelial tumour cells associated with papillomavirus infection.

Vet J 2016 Jun 11;212:44-7. Epub 2016 Jan 11.

Dipartimento di Medicina Veterinaria e Produzioni Animali, Settore di Malattie Infettive, Università di Napoli Federico II, Napoli, Italy. Electronic address:

Embryonic stem cell-expressed Ras (ERas) encodes a constitutively active form of guanosine triphosphatase (GTPase) that binds to and activates phosphatidylinositol 3 kinase (PI3K), which in turn phosphorylates and activates downstream targets such as Akt. The current study evaluated ERas regulation and expression in papillomavirus-associated urothelial tumours in cattle grazing on lands rich in bracken fern. ERas was found upregulated and overexpressed by PCR, real time PCR and Western blot. Furthermore, protein overexpression was also confirmed by immunohistochemistry. ERas was found to interact physically and colocalise with the activated platelet derived growth factor β receptor (PDGFβR) by coimmunoprecipitation and laser scanning confocal investigations. Phosphorylation of Akt, a downstream effector both of ERas and PDGFβR, appeared to be increased in urothelial tumour cells. Altogether, these data indicate that ERas/PDGFβR complex could play a role in the pathogenesis of bovine papillomavirus-associated bladder neoplasia.
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http://dx.doi.org/10.1016/j.tvjl.2016.01.004DOI Listing
June 2016

ATP Sensitive Potassium Channels in the Skeletal Muscle Function: Involvement of the KCNJ11(Kir6.2) Gene in the Determination of Mechanical Warner Bratzer Shear Force.

Front Physiol 2016 10;7:167. Epub 2016 May 10.

Department of Veterinary Medicine, University of Bari Aldo Moro Bari, Italy.

The ATP-sensitive K(+)-channels (KATP) are distributed in the tissues coupling metabolism with K(+) ions efflux. KATP subunits are encoded by KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1), and ABCC9 (SUR2) genes, alternative RNA splicing give rise to SUR variants that confer distinct physiological properties on the channel. An high expression/activity of the sarco-KATP channel is observed in various rat fast-twitch muscles, characterized by elevated muscle strength, while a low expression/activity is observed in the slow-twitch muscles characterized by reduced strength and frailty. Down-regulation of the KATP subunits of fast-twitch fibers is found in conditions characterized by weakness and frailty. KCNJ11 gene knockout mice have reduced glycogen, lean phenotype, lower body fat, and weakness. KATP channel is also a sensor of muscle atrophy. The KCNJ11 gene is located on BTA15, close to a QTL for meat tenderness, it has also a role in glycogen storage, a key mechanism of the postmortem transformation of muscle into meat. The role of KCNJ11 gene in muscle function may underlie an effect of KCNJ11 genotypes on meat tenderness, as recently reported. The fiber phenotype and genotype are important in livestock production science. Quantitative traits including meat production and quality are influenced both by environment and genes. Molecular markers can play an important role in the genetic improvement of animals through breeding strategies. Many factors influence the muscle Warner-Bratzler shear force including breed, age, feeding, the biochemical, and functional parameters. The role of KCNJ11gene and related genes on muscle tenderness will be discussed in the present review.
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http://dx.doi.org/10.3389/fphys.2016.00167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862255PMC
May 2016

Tumour-associated macrophages correlate with microvascular bed extension in colorectal cancer patients.

J Cell Mol Med 2016 07 22;20(7):1373-80. Epub 2016 Apr 22.

Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, 'Giovanni Paolo II', Bari, Italy.

Tumour-associated macrophages (TAMs) represent pivotal components of tumour microenvironment promoting angiogenesis, tumour progression and invasion. In colorectal cancer (CRC), there are no conclusive data about the role of TAMs in angiogenesis-mediated tumour progression. In this study, we aimed to evaluate a correlation between TAMs, TAM immunostained area (TAMIA) microvascular density (MVD), endothelial area (EA) and cancer cells positive to VEGF-A (CCP-VEGF-A) in primary tumour tissue of locally advanced CRC patients undergone to radical surgery. A series of 76 patients with CRC were selected and evaluated by immunohistochemistry and image analysis. An anti-CD68 antibody was employed to assess TAMs and TAMIA expression, an anti-CD34 antibody was utilized to detect MVD and EA expression, whereas an anti-VEGF-A antibody was used to detect CCP-VEGF-A; then, tumour sections were evaluated by image analysis methods. The mean ± S.D. of TAMs, MVD and CCP-VEGF-A was 65.58 ± 21.14, 28.53 ± 7.75 and 63% ± 37%, respectively; the mean ± S.D. of TAMIA and EA was 438.37 ± 124.14μ(2) and 186.73 ± 67.22μ(2) , respectively. A significant correlation was found between TAMs, TAMIA, MVD and EA each other (r ranging from 0.69 to 0.84; P ranging from 0.000 to 0.004). The high level of expression of TAMs and TAMIA in tumour tissue and the significant correlation with both MVD and EA illustrate that TAMs could represent a marker that plays an important role in promoting angiogenesis-mediated CRC. In this context, novel agents killing TAMs might be evaluated in clinical trials as a new anti-angiogenic approach.
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http://dx.doi.org/10.1111/jcmm.12826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929299PMC
July 2016

Mast cells positive to tryptase and tumour-associated macrophages correlate with angiogenesis in locally advanced colorectal cancer patients undergone to surgery.

Expert Opin Ther Targets 2016 16;20(5):533-40. Epub 2016 Mar 16.

c Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology , National Cancer Research Centre, 'Giovanni Paolo II' , Bari , Italy.

Objective: The density of mast cells positive to tryptase (MCDPT) and tumor-associated macrophages (TAMs) were evaluated in a series of 87 patients with stage B and C colorectal cancer who had undergone radical surgery.

Methods: MCDPT, TAMs, microvascular density (MVD), endothelial area (EA) and CD8(+) tumor infiltrating lymphocytes (CD8(+) TILs) were evaluated in tumor tissue samples by immunohistochemistry and image analysis. Each of the above parameters was correlated with the others and with the main clinico-pathological features.

Results: A significant correlation between MCDPT, TAMs, MVD and EA was found by Pearson t-test analysis. With special references to the clinico-pathological features a minimal correlation using univariate analysis was found but it was not retained at multivariate analysis.

Conclusions: Our data suggest that MCDPT and TAMs are linked in the tumor microenvironment and play a role in CRC angiogenesis in a synergistic manner. The assessment of the combination MCDPT and TAMs could be evaluated as a target of novel anti-angiogenic therapies in colorectal cancer patients.
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http://dx.doi.org/10.1517/14728222.2016.1158811DOI Listing
December 2016

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients.

Oncol Lett 2015 Aug 27;10(2):967-971. Epub 2015 May 27.

Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, 'Giovanni Paolo II', Bari 70124, Italy.

Previous experimental and clinical data have indicated that tumour cell proliferation is associated with angiogenesis; in addition, an increased microvascular density (MVD) of tumours has been associated with poor prognosis in solid and haematological malignancies. However, limited data exists regarding the association between tumour cell proliferation and angiogenesis in primary tumour tissue from pancreatic ductal adenocarcinoma (PDAC) patients; therefore, the present study aimed to investigate this association. A series of 31 PDAC patients with stage Tumour (T) Node (N) Metastasis (M) were recruited into the present study and subsequently underwent surgery. PDAC tissue and adjacent normal tissue (ANT), resected during surgery, were evaluated using immunohistochemistry and image analysis methods to determine MVD, endothelial area (EA) and Ki-67 expression, which is an indicator of cell proliferation rate. The results demonstrated a correlation between the above parameters with each other as well as the main clinico-pathological features of PDAC. Significant differences were identified in MVD, EA and Ki-67 proliferation index between PDAC and ANT. It was demonstrated that MVD, EA and Ki-67 proliferation index were significantly correlated with each other in tumour tissue (r=0.69-0.81; P=0.001-0.003). However, no other significant correlations were identified. These data therefore suggested that angiogenesis and cell proliferation rate were significantly increased in PDAC compared with ANT, which provides a biological basis for the potential use of novel combinations of angiogenesis inhibitors and anti-proliferative chemotherapeutic drugs in the treatment of PDAC.
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http://dx.doi.org/10.3892/ol.2015.3286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509049PMC
August 2015

Infiltrating mast cells correlate with angiogenesis in bone metastases from gastric cancer patients.

Int J Mol Sci 2015 Feb 2;16(2):3237-50. Epub 2015 Feb 2.

Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", viale Orazio Flacco 65, Bari 70124, Italy.

While gastric cancer is a well established angiogenesis driven tumor, no data has been published regarding angiogenesis stimulated by mast cells (MCs) positive for tryptase in bone metastases from gastric cancer patients (BMGCP). It is well established that MCs play a role in immune responses and more recently it was demonstrated that MCs have been involved in tumor angiogenesis. We analyzed infiltrating MCs and neovascularization in BMGCP diagnosed by histology. A series of 15 stage T3-4N2-3M1 (by AJCC for Gastric Cancer Staging 7th Edition) BMGCP from bone biopsies were selected. Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of MCs density positive to tryptase (MCDPT), MCs area positive to tryptase (MCAPT), microvascular density (MVD) and endothelial area (EA). A significant correlation between MCDPT, MCAPT, MVD and EA groups to each other was found by Pearson and t-test analysis (r ranged from 0.68 to 0.82; p-value ranged from 0.00 to 0.02). Our very preliminary data suggest that infiltrating MCs positive for tryptase may play a role in BMGCP angiogenesis, and could be further evaluated as a novel target of anti-angiogenic therapy.
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http://dx.doi.org/10.3390/ijms16023237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346892PMC
February 2015