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Possible biological and translational significance of mast cells density in colorectal cancer

World Journal of Gastroenterology 2014年第27期20卷 8910-8920页

作者： Ilaria Marech Michele Ammendola Claudia Gadaleta Nicola Zizzo Caroline Oakley Cosmo Damiano Gadaleta girolamo ranieri Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre Istituto Tumori "Giovanni Paolo Ⅱ" 70124 BariItaly Department of Clinical Surgery University of Catanzaro "Magna Graecia" Medical School 88100 Catanzaro Italy Department of Pathology Veterinary Medical School University of Bari Valenzano 70010 Bari Italy

Mast cells (MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated (mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor (c-KitR) and tryptase (an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density (MCD) role in colorectal cancer (CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors (imatinib, masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) with the aim to prevent CRC progression.

关键词： Tryptase Mast cell density Proteinase-activated receptor-2 c-Kit receptor Vascular endothelial growth factor Angiogenesis Colorectal cancer Tumor progression Tryptase inhibitors c-Kit receptor tyrosine kinase inhibitors

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Molecular targeting agents associated with transarterial chemoembolization or radiofrequency ablation in hepatocarcinoma treatment

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World Journal of Gastroenterology 2014年第2期20卷 486-497页

作者： girolamo ranieri Ilaria Marech Vito Lorusso Veronica Goffredo Angelo Paradiso Domenico Ribatti Cosmo Damiano Gadaleta Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research CentreCancer Institute "Giovanni Paolo Ⅱ"70124 BariItaly Medical Oncology Unit National Cancer Research CentreCancer Institute "Giovanni Paolo Ⅱ"70124 BariItaly Medical Oncology with Experimental Unit National Cancer Research CentreCancer Institute "Giovanni Paolo Ⅱ"70124 BariItaly Department of Basic Medical Sciences Neurosciences and Sensory OrgansSection of Human Anatomy and HistologyUniversity of Bari70124 BariItaly

Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the *** to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablation(RFA),while patients with intermediate stage HCC are usually treated by transarterial chemoembolization(TACE).TACE and RFA induce a transient devascularisation effect followed by strong neoangiogenic *** fact,after these procedures,it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A,which might contribute to accelerated progression in patients with incomplete *** studies have demonstrated that MAP-kinase and AKT pathways,in addition to neo-angiogenesis,have an important role in the development of *** advanced HCC,anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical ***,a number of clinical studies are ongoing testing these agents in combination with TACE or *** this paper,we have reviewed the most recent preclinical and clinical results of such trials.

关键词： Hepatocellular carcinoma Molecular targeting agents Angiogenesis Chemoembolization therapeutic Radiofrequency treatment Sorafenib

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Vascular endothelial growth factor and tryptase changes after chemoembolization in hepatocarcinoma patients

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World Journal of Gastroenterology 2015年第19期21卷 6018-6025页

作者： girolamo ranieri Michele Ammendola Ilaria Marech Annamaria Laterza Ines Abbate Caroline Oakley Angelo Vacca Rosario Sacco Cosmo Damiano Gadaleta Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre Department of Medical and Surgical Sciences Clinical Surgery Unit University of "Magna Graecia" Department of Experimental Oncology Laboratory of Analyses Cancer Institute "Giovanni Paolo II" Department of Internal Medicine and Clinical Oncology University of Bari Medical School

AIM: To evaluate vascular endothelial growth factor(VEGF) and tryptase in hepatocellular cancer(HCC)before and after trans-arterial chemoembolization(TACE).METHODS: VEGF and tryptase serum concentrations were assessed from 71 unresectable HCC patients before and after hepatic TACE performed by binding DC-Beads?to doxorubicin. VEGF levels were examined for each serum sample using the Quantikine Human VEGF-enzyme-linked immuno-absorbent assay(ELISA),whereas tryptase serum concentrations were assessed for each serum sample by means of fluoro-enzyme immunoassay(FEIA) using the Uni-CAP100 *** between serum VEGF and tryptase values before and after TACE were evaluated using Student t test. Person's correlation was used to assess the degree of association between the two ***: VEGF levels and serum tryptase in HCCpatients before TACE had a mean value and standard deviation(SD) of 114.31 ± 79.58 pg/mL and 8.13± 3.61 μg/L, respectively. The mean levels and SD of VEGF levels and serum tryptase in HCC patients after TACE were 238.14 ± 109.41 pg/mL and 4.02 ±3.03 μg/L. The changes between the mean values of concentration of VEGF and tryptase before treatment and after treatment was statistically significant(P <0.000231 and P < 0.00124, by Wilcoxon-Mann-Whitney respectively). A significant correlation between VEGF levels before and after TACE and between tryptase levels before and after TACE was demonstrated(r =0.68, P = 0.003; r = 0.84, P = 0.000 respectively).CONCLUSION: Our pilot results suggest that the higher serum VEGF levels and the lower tryptase levels following TACE may be potential biomarkers changing in response to therapy.

关键词： Serum levels Tryptase Vascular endothelialgrowth factor Hepatocellular cancer Chemoembolization

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Hyperthermic intraperitoneal chemotherapy and colorectal cancer:From physiology to surgery

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World Journal of Clinical Cases 2022年第30期10卷 10852-10861页

作者： Giorgio Ammerata Rosalinda Filippo Carmelo Laface Riccardo Memeo Leonardo Solaini Davide Cavaliere Giuseppe Navarra girolamo ranieri Giuseppe Currò Michele Ammendola Department Digestive Surgery UnitUniversity“Magna Graecia”Medical SchoolCatanzaro 88100Italy Interventional Oncology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre“Giovanni Paolo Ⅱ”Bari 70124Italy Hepato-Biliary and Pancreatic Surgical Unit “F.Miulli”HospitalAcquaviva delle FontiBari 70124Italy Department of Medical and Surgical Sciences University of BolognaForlì40126Italy Department of General and Oncologic Surgery Morgagni-Pierantoni HospitalForlì47121Italy Department of Human Pathology of Adult and Evolutive Age Surgical Oncology Division“G.Martino”HospitalUniversity of MessinaMessina 98122Italy

The pursuit of this paper is to collect principal reviews and systematic reviews about hyperthermic intraperitoneal chemotherapy(HIPEC) and cytoreductive surgery(CRS) used in colorectal cancer(CRC).We focus on principal biological aspects of CRC,hyperthermia effects,and surgical *** searched PubMed/MEDLINE for the principal reviews and systematic reviews published from 2010 to 2021 regarding the bimodal treatment(CRS + HIPEC) against local and advanced *** the literature,from several studies,it seems that the efficacy of bimodal treatment with an accurate CRS can extend overall *** these studies,there are not still any straight guidelines more detailed and scheduled about the use of combined treatment in patients with *** if the concept is still not very clear and shared,after a careful evaluation of the published data,and after some technical and pathophysiological descriptions,we concluded that it is possible to improve the overall survival and quality of life and to reduce the tumor relapse in patients affected by locally advanced(pT4) CRC with peritoneal metastases.

关键词： Hyperthermic intraperitoneal chemotherapy Colorectal cancer Peritoneum Cytoreductive surgery

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Targeting mast cells in gastric cancer with special reference to bone metastases

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World Journal of Gastroenterology 2015年第37期21卷 10493-10501页

作者： Christian Leporini Michele Ammendola Ilaria Marech Giuseppe Sammarco Rosario Sacco Cosmo Damiano Gadaleta Caroline Oakley Emilio Russo Giovambattista De Sarro girolamo ranieri Department of Health Science Clinical Pharmacologyand Pharmacovigilance Unit and Pharmacovigilance’s Centre Calabria Region University of Catanzaro "Magna Graecia"Medical School Department of Medical and Surgery Sciences Clinical Surgery Unit University of Catanzaro "Magna Graecia" Medical School Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre

Bone metastases from gastric cancer(GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells(MCs) positive to tryptase(MCPT) in primary gastric tumor angiogenesis. Recently,we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating,peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents,such as MCs tryptase inhibitors(gabexate mesylate,nafamostat mesylate) or c-KitR tyrosine kinase inhibitors(imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patientsaffected by bone metastases.

关键词： Bone metastases Gastric cancer receptor activator

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H pylori status and angiogenesis factors in human gastric carcinoma

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World Journal of Gastroenterology 2006年第34期12卷 5465-5472页

作者： Anita Mangia Annalisa Chiriatti girolamo ranieri Ines Abbate Maria Coviello Giovanni Simone Francesco Alfredo Zito Severino Montemurro Antonello Rucci Alfredo Di Leo Stefania Tommasi Pasquale Berloco Jian Ming Xu Angelo Paradiso Clinical Experimental Oncology Laboratory National Cancer Institute 70126 Bari Italy Interventional Radiology Unit National Cancer Institute 70126 Bari Italy Chemical-Clinical-Microbiology and Immunology Laboratory Unit National Cancer Institute70126 Bari Italy Histopathology Unit National Cancer Institute 70126 Bari Italy Gastroenterology Surgical Unit National Cancer Institute Bari Italy Department of Emergency and Organ Transplantation Section of Gastroenterology University of Bari Italy Laboratory of Biochemistry IRCCS 'Saverio de Bellis' Castellana Grotte (BA) Italy Department of Gastrointestinal Cancer Beijing 307 Hospital Cancer Center Beijing China

AIM： To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density （MVD）, thymidine phosphorylase （TP）, vascular endothelial growth factor receptor-1 （VEGF-R1）, p53 and circulating VEGF levels. METHODS： Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin （vacA） and the cytotoxin-associated gene （cagA） amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS： A total of 69% of patients were positive for circulating IgG antibodies against Hpylori. cagA-positive H pylor/strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA （P = 0.0001）. MVD was significantly correlated with both tumor VEGF expression （r = 0.361, P = 0.009） and serum VEGF levels （r = -0.347, P = 0.041）.Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level （P = 0.026）. CONCLUSION： H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.

关键词： H pylori Gastric carcinoma Angiogenesis

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Modulated electro-hyperthermia in stage III and IV pancreatic cancer:Results of an observational study on 158 patients

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World Journal of Clinical Oncology 2021年第11期12卷 1064-1071页

作者： Giammaria Fiorentini Donatella Sarti girolamo ranieri Cosmo Damiano Gadaleta Caterina Fiorentini Carlo Milandri Andrea Mambrini Stefano Guadagni Department of Onco-Hematology Azienda Ospedaliera“Ospedali Riuniti Marche Nord”Pesaro 61122Italy Oncology Department Ospedale S.Maria Della MisericordiaASUR1Urbino 61029Italy Interventional and Integrated Medical Oncology National Cancer Research CentreIRCCS Istituto Tumori"Giovanni Paolo II"Bari 70124Italy Department of Medical Biothecnologies Division of CardiologyUniversity Hospital of SienaSiena 53100Italy Medical Oncology Unit San Donato HospitalArezzo 52100Italy Department of Oncology-ASL Toscana Nord Ovest Massa Carrara HospitalMassa 54100Italy Applied Clinical Sciences and Biotechnology Section of General SurgeryUniversity of L’AquilaL’Aquila 67100Italy

BACKGROUND An increasing number of studies report the beneficial effects of regional hyperthermia in association with chemotherapy(CHT)and radiotherapy for the treatment of pancreatic cancer;in particular,the use of modulated electrohyperthermia(mEHT)results in increased survival and tumor *** To compare outcomes of CHT alone or in association with mEHT for the treatment of stage III and IV pancreatic *** This was an observational retrospective study;data were collected for patients with stage III-IV pancreatic cancer that were treated with CHT alone or in combination with mEHT from 2003 to 2019.A total of 158 patients were included in the study out 270 patients screened in four Italian hospitals;58(37%)of these received CHT+mEHT and 100(63%)*** was mainly gemcitabine-based regimens in both *** Overall(19.5 mo vs 11.02 mo,P<0.001)and progression-free(12 mo vs 3 mo,P<0.001)survival were better for the CHT+mEHT group compared to the CHT *** association of mEHT resulted also in an improvement of tumor response with disease control rate 95%vs 58%(P<0.001)at 3 *** was comparable in the two study groups,and mEHT related adverse events were limited in 8 patients presenting G1-2 skin *** The addition of mEHT to systemic CHT improved overall and progression-free survival and local tumor control with comparable toxicity.

关键词： Modulated electro-hyperthermia Locally advanced pancreatic cancer Tumor response Survival

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Precision pulmonary trans-arterial chemoembolization（PPTACE） plus RFA for lung neoplasms:safety and feasibility

Precision pulmonary trans-arterial chemoembolization（PPTACE...

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2009年世界肿瘤介入学术大会

作者： Cosmo Gadaleta Annamaria Catino Giuseppe Rubini Vito Fazio girolamo ranieri Gennaro Gadaleta-Caldarola Antonio Cramarossa Eugenio Canniello Francesco Armenise Angela Gaudiano Gaetano Martinelli Elena Ludovico Gianluca Vinciarelli Giuseppe Laricchia Veronica Goffredo Vittorio Mattioli Oncology Institute Bari-Italy Nuclear Medicine University of Bari-Italy Miulli Hospital Acquaviva d.f.-Italy

＜正＞Objectives:The study aimed to evaluate the feasibility and safety of precision pulmonary arterial chemoembolization （PPTACE）followed by percutaneous RFA in patients with unresectable lung neoplasms. Patients and methods:From November 2007 to April 2009,twelve patients（5 male,7 female,median age 57）and 20 nodules were treated in 14 sessions.

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Ferrierite vs. γ-Al_2O_3: The superiority of zeolites in terms of water-resistance in vapour-phase dehydration of methanol to dimethyl ether

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Journal of Energy Chemistry 2019年第3期28卷 162-169页

作者： Enrico Catizzone Massimo Migliori Antonio Purita girolamo Giordano Department of Environmental and Chemical Engineering University of Calabria

The catalytic conversion of methanol to dimethyl ether(DME) over a series of home-made FER-type zeolites having different acidities and commercial γ-Al_2O_3 has been studied with the aim to understand the impact of adding water in the reactant stream on the catalytic behavior on investigated materials. Cofeeding water with methanol, the alcohol conversion was slightly reduced over the investigated zeolites while the catalytic activity of γ-Al_2O_3, the traditional catalyst of MeOH-to-DME conversion, was strongly inhibited. It was also found that, for the investigated zeolites, both the amount and the initial deposition rate of the coke formed during the reaction were reduced when water was co-fed with methanol while no significant effects on both methanol conversion and DME selectivity were observed under the investigated conditions.

关键词： Ferrierite Zeolites Methanol dehydration Dimethyl ether Coke

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The effect of FER zeolite acid sites in methanol-to-dimethyl-ether catalytic dehydration

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Journal of Energy Chemistry 2017年第3期26卷 406-415页

作者： Enrico Catizzone Alfredo Aloise Massimo Migliori girolamo Giordano Department of Environmental and Chemical Engineering University of CalabriaVia P.BucciCubo 42aI-87036 RendeCSItaly

In this paper, the effect of acidity of zeolites with FER framework was studied in the methanol dehydration to dimethyl ether reaction, by comparing catalysts with different Si/Al ratios(namely 8, 30 and60). The aim of this work was to investigate how the acid sites concentration, strength, distribution and typology(Br?nsted and Lewis) affect methanol conversion, DME selectivity and coke formation. It was found that the aluminium content affects slightly acid sites strength whilst a relevant effect on acid sites concentration and distribution(Br?nsted/Lewis) was observed as 24% of Lewis sites were found on Alrichest samples, whilst less than 10% of Lewis acid sites were observed on FER at higher Si/Al ratio. All the investigated catalyst samples showed a selectivity toward DME always greater than 0.9 and samples with the lowest Si/Al ratio exhibit the best performances in terms of methanol conversion, approaching the theoretical equilibrium value(around 0.85) at temperatures below 200 °C. Turnover-frequency analysis suggests that this result seems to be related not only to the higher amount of acid sites but also that the presence of Lewis acid sites may play a significant role in converting methanol. On the other hand, the presence of Lewis acid sites, combined with a high acidity, promote the formation of by-products(mainly methane) and coke deposition during the reaction. As final evidence, all the investigated catalysts exhibit very high resistance to deactivation by coke deposition, over 60 h continuous test, and a GC–MS analysis of the coke deposited on the catalyst surface reveals tetra-methyl benzene as main component.

关键词： Methanol dehydration Dimethyl ether Lewis acid sites FER zeolite Coke formation

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