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Immune response in COVID-19:addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1759-1768页

作者： michele catanzaro Francesca Fagiani Marco Racchi Emanuela Corsini Stefano Govoni Cristina Lanni Department of Drug Sciences(Pharmacology Section) University of PaviaV.le Taramelli 1427100 PaviaItaly Scuola Universitaria Superiore IUSS Pavia P.zza Vittoria1527100 PaviaItaly Laboratory of Toxicology Department of Environmental and Political SciencesUniversitàDegli Studi di MilanoVia Balzaretti 920133 MilanoItaly

To date,no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive ***,based on the fast and global spread of the virus,urgent investigations are warranted in order to develop preventive and therapeutic *** this regard,treatments addressing the immunopathology of SARS-CoV-2 infection have become a major ***,while a rapid and well-coordinated immune response represents the first line of defense against viral infection,excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic *** studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 *** particular,the massive cytokine and chemokine release,the so-called“cytokine storm”,clearly reflects a widespread uncontrolled dysregulation of the host immune *** the prospective of counteracting cytokine storm is compelling,a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 *** identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be ***,given the key role of the immune system in COVID-19,a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.

关键词： drugs impaired storm

Diagnostic accuracy of enhanced liver fibrosis test to assess liver fibrosis in patients with chronic hepatitis C

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Hepatobiliary & Pancreatic Diseases International 2013年第5期12卷 500-507页

作者： Roberto catanzaro michele Milazzo Silvia Arona Chiara Sapienza Dario Vasta Domenico Arcoria Francesco Marotta Department of Medical and Pediatric Sciences Institute of Internal Medicine "A. Francaviglia"Section of Gastro-enterologyUniversity of Catania"G. Rodolico" Hospital Laboratory analysis "MedLab-Analisi Cliniche" Specialist in diabetes and metabolic diseases ReGenera Research Group for Aging Intervention

BACKGROUND:The prognosis and clinical management of patients with chronic liver diseases are closely related to the severity of liver *** biopsy is considered the gold standard for the staging of liver ***,it is an invasive test sometimes related to *** study aimed to assess the diagnostic value of enhanced liver fibrosis(ELF) test to predict liver fibrosis in patients with chronic hepatitis ***:This study included 162 patients with liver disease and 67 healthy *** acid,tissue inhibitor of matrix metalloproteinase type 1,and amino-terminal propeptide type III procollagen were measured by enzymelinked immunosorbent assay with the ELF test ADVIA Centaur(Siemens Healthcare Diagnostics Inc.).Fibrosis stage was determined using the Metavir scoring ***:In our study,for the diagnosis of significant fibrosis(Metavir F≥2) a cut-off value >7.72 provides a sensitivity of 93.0% and a specificity of 83.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,93.3%,81.0%,93.3%,and 81.0%,respectively(P9.3 provides a sensitivity of 93.0% and a specificity of 86.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,79.1%,90.8%,75.6%,and 92.3%,respectively(P<0.001).CONCLUSIONS:The ELF test is a promising non-invasive method for assessing liver fibrosis in patients with chronic hepatitis *** is effective in the diagnosis of both fibrosis and cirrhosis.

关键词： enhanced liver fibrosis test non-invasive diagnosis liver fibrosis blood marker

Close relationship between mediators of inflammation and pancreatic cancer:Our experience

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World Journal of Gastroenterology 2024年第23期30卷 2927-2930页

作者： Francesca Vescio michele Ammendola Giuseppe Currò Silvia Curcio Department General Surgery UnitUniversity“Magna Graecia”Medical SchoolUniversity Hospital“R.Dulbecco”Catanzaro 88100Italy Science of Health Department Digestive Surgery UnitUniversity“Magna Graecia”Medical SchoolUniversity Hospital“R.Dulbecco”Catanzaro 88100Italy

In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic *** of the pancreas remains one of the deadliest cancer *** highest incidence and mortality rates of pancreatic cancer are found in developed *** of pancreatic cancer incidence and mortality vary considerably worldwide.A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this *** tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this *** this editorial,we highlight the foundational studies that have driven our understanding of these *** our experimental center,we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic *** focused on the role of mast cells(MCs).MCs contain pro-angiogenic factors,including tryptase,that are associated with increased angiogenesis in various *** this editorial,we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal *** assessment includes the density of c-Kit receptor-positive MCs,the density of tryptase-positive MCs,the area of tryptasepositive MCs,and angiogenesis in terms of microvascularization density.

关键词： Mast cells C-Kit receptor Tryptase Angiogenesis Microvascular density Endothelial area Pancreatic tumor tissue Adjacent normal tissue

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

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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

A new era for hepatocellular carcinoma

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Hepatobiliary Surgery and Nutrition 2023年第1期12卷 135-136页

作者： Riccardo Memeo Antonio Rosario Pisani michele Ammendola Nicola de’Angelis Riccardo Inchingolo Division of Hepato-Pancreato-Biliary Surgery “F.Miulli”General HospitalAcquaviva delle FontiBariItaly Nuclear Medicine Unit Interdisciplinary Department of MedicineUniversity of Bari‘Aldo Moro’BariItaly Science of Health Department Digestive Surgery UnitUniversity“Magna Graecia”Medical SchoolCatanzaroItaly Unit of Colorectal and Digestive Surgery DIGEST DepartmentBeaujon University Hospital(AP-HP)University Paris CiteClichyFrance Interventional Radiology Unit “F.Miulli”Regional General HospitalAcquaviva Delle FontiBariItaly

Hepatocellular carcinoma(HCC)is one of the most frequent cancers worldwide among patients with cirrhosis,and its management and treatment is in continuous evolution due to the introductions of new therapeutic *** represents most common primary malignancy of the liver,developing in 90%of cases of un underlying liver disease(1)[chronic HBV and HCV hepatitis,dysmetabolic liver disease].

关键词： Hepatocellular carcinoma(HCC) guidelines Consensus statement Japan Society of Hepatology

Harnessing the value of TCTP in breast cancer treatment resistance: an opportunity for personalized therapy

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Cancer Drug Resistance 2023年第3期6卷 447-467页

作者： Gianluca Santamaria Mario Cioce Antonia Rizzuto Vito michele Fazio Giuseppe Viglietto Maria Lucibello Department of Experimental and Clinical Medicine “Magna Graecia”University of CatanzaroCatanzaro 88100Italy Department of Medicine Laboratory of Molecular Medicine and BiotechnologyUniversity Campus Bio-Medico of RomeRome 00128Italy Institute of Translational Pharmacology National Research Council of Italy(CNR)Rome 00133Italy Department of Medical and Surgical Sciences “Magna Graecia”University of CatanzaroCatanzaro 88100Italy Department of Biomedical Sciences Institute for Biomedical Research and InnovationNational Research Council of Italy(CNR)Catanzaro 88100Italy

Early identification of breast cancer (BC) patients at a high risk of progression may aid in therapeutic and prognostic aims. This is especially true for metastatic disease, which is responsible for most cancer-related deaths. Growing evidence indicates that the translationally controlled tumor protein (TCTP) may be a clinically relevant marker for identifying poorly differentiated aggressive BC tumors. TCTP is an intriguing protein with pleiotropic functions, which is involved in multiple signaling pathways. TCTP may also be involved in stress response, cell growth and proliferation-related processes, underlying its potential role in the initiation of metastatic growth. Thus, TCTP marks specific cancer cell sub-populations with pronounced stress adaptation, stem-like and immune-evasive properties. Therefore, we have shown that in vivo phospho-TCTP levels correlate with the response of BC cells to anti-HER2 agents. In this review, we discuss the clinical relevance of TCTP for personalized therapy, specific TCTP-targeting strategies, and currently available therapeutic agents. We propose TCTP as an actionable clinically relevant target that could potentially improve patient outcomes.

关键词： Breast cancer metastasis TCTP stem cells therapy resistance biomarker

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

Metabolic syndrome in White-European men presenting for secondary couple＇s infertility： an investigation of the clinical and reproductive burden

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Asian Journal of Andrology 2017年第3期19卷 368-373页

作者： Eugenio Ventimiglia Paolo Capogrosso Alessandro Serino Luca Boeri michele Colicchia Giovanni La Croce Roberta Scano Enrico Papaleo Rocco Damiano Francesco Montorsi Andrea Salonia Division of Experimental Oncology Unit of Urology URI IRCCS Ospedale San Raffaele 20132 Milan Italy University Vita-Salute San Raffaele 20132 Milan Italy Infertility Unit Unit of Obstetrics/Gynecology IRCCS Ospedale San Raffaele 20132 Milan Italy Research Doctorate Program in Urology Magna Graecia University 88020 Catanzaro Italy.

We aimed to determine the impact of metabolic syndrome （MetS） on reproductive function in men with secondary infertility, a condition that has received relatively little attention from researchers. Complete demographic, clinical, and laboratory data from 167 consecutive secondary infertile men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index （CCI; categorised 0 vs I vs 2 or higher）. NCEP-ATP III criteria were used to define MetS. Semen analysis values were assessed based on the 2010 World Health Organization （WHO） reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and MetS. MetS was found in 20 （12%） of 167 men. Patients with MetS were older （P 〈 0.001） and had a greater BMI （P 〈 0.001） compared with those without MetS. MetS patients had lower levels of total testosterone （P = 0.001）, sex hormone-binding globulin, inhibin B, and anti-MOIlerian hormone （all P 〈 0.03）, and they were hypogonadal at a higher prevalence （P = 0.01） than patients without MetS. Moreover, MetS patients presented lower values of semen volume, sperm concentration, and sperm normal morphology （all P≤0.03）. At multivariate logistic regression analysis, no parameters predicted sperm concentration, normal sperm morphology, and total progressive motility. Our data show that almost 1 of 8 White-European men presenting for secondary couple＇s infertility is diagnosed with MetS. MetS was found to be associated with a higher prevalence of hypogonadism, decreased semen volume, decreased sperm concentration, and normal morphology in a specific cohort of White-European men.

关键词： infertility metabolic syndrome sperm count

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