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Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas

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Cancer Biology & Medicine 2021年第2期18卷 502-516页

作者： Giacomo Miserocchi Claudia Cocchi Alessandro De Vita chiara Liverani chiara Spadazzi Sebastiano Calpona Giandomenico Di Menna Massimo Bassi Giuseppe Meccariello Giovanni De Luca Angelo Campobassi maria Maddalena Tumedei Alberto Bongiovanni Valentina Fausti Franco Cotelli Toni Ibrahim Laura Mercatali Osteoncology and Rare Tumors Center IRCCS Istituto Romagnolo per lo Studio dei Tumori(IRST)“Dino Amadori”Meldola 47014Italy Maxillofacial Surgery Unit Bufalini HospitalCesena 47521Italy Department of Head-Neck Surgery OtolaryngologyHead-Neck and Oral Surgery UnitMorgagni Pierantoni HospitalForlì47121Italy Pathology Unit “Bufalini”HospitalAUSL RomagnaCesena 47521Italy Biosciences Laboratory IRCCS Istituto Romagnolo per lo Studio dei Tumori(IRST)“Dino Amadori”Meldola 47014Italy Department of Biosciences Universitàdegli Studi di MilanoMilan 20133Italy

Objective:Squamous cell carcinoma(SCC)represents the most common histotype of all head and neck malignancies and includes oropharyngeal squamous cell carcinoma(OSCC),a tumor associated with different clinical outcomes and linked to human papilloma virus(HPV)*** research has few available in vitro models with which to study the different pathophysiological behavior of *** present study proposes a 3-dimensional(3 D)biomimetic collagen-based scaffold to mimic the tumor microenvironment and the crosstalk between the extracellular matrix(ECM)and cancer ***:We compared the phenotypic and genetic features of HPV-positive and HPV-negative OSCC cell lines cultured on common monolayer supports and on *** also explored cancer cell adaptation to the 3 D microenvironment and its impact on the efficacy of drugs tested on cell lines and primary ***:HPV-positive and HPV-negative cell lines were successfully grown in the 3 D model and displayed different collagen fiber *** 3 D cultures induced an increased expression of markers related to epithelial–mesenchymal transition(EMT)and to matrix interactions and showed different migration behavior,as confirmed by zebrafish embryo *** expression of hypoxia-inducible factor 1α(1α)and glycolysis markers were indicative of the development of a hypoxic microenvironment inside the scaffold ***,the 3 D cultures activated drug-resistance signaling pathways in both cell lines and primary ***:Our results suggest that collagen-based scaffolds could be a suitable model for the reproduction of the pathophysiological features of ***,3 D architecture appears capable of inducing drug-resistance processes that can be studied to better our understanding of the different clinical outcomes of HPV-positive and HPV-negative patients with OSCCs.

关键词： Oropharyngeal squamous cell carcinoma collagen biomimetic scaffold zebrafish drug-resistance primary culture

“Starry liver”-Von Meyenburg complex clinical case presentation and differential diagnosis discussion:A case report

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World Journal of Hepatology 2022年第7期14卷 1520-1527页

作者： Kateryna Priadko Marco Niosi Luigi maria Vitale chiara De Sio Marco Romano Ilario De Sio Department of Precision Medicine and Hepato-Gastroenterology Unit University Hospital and Universitàdegli Studi della Campania Luigi VanvitelliNaples 80138Italy Internal Medicine Unit Camilliani HospitalCasoria 80026Italy

BACKGROUND Von Meyenburg complex(VMC)(i.e.,biliary hamartoma)is a rare congenital disorder characterized by multiple dilated cystic bile ducts,without clear trends in sex or age *** to the low number of published cases and the lack of recognized guidelines,the management of such patients remains a clinical *** SUMMARY We present a case of symptomatic VMC that was diagnosed after imaging and histopathological *** the patient’s condition,a conservative treatment strategy was ***,laboratory,and clinical follow-up demonstrated the stable condition of the patient receiving conservative *** VMC is a potentially non-life threatening condition,but its recognition is crucial for the management of patients.

关键词： Biliary hamartoma Von Meyenburg complex Liver polycystic disease Ultrasonography imaging Magnetic resonance imaging Case report

Inflammatory bowel diseases and human reproduction:A comprehensive evidence-based review

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World Journal of Gastroenterology 2014年第23期20卷 7123-7136页

作者： Stefano Palomba Giuliana Sereni Angela Falbo Marina Beltrami Silvia Lombardini maria chiara Boni Giovanni Fornaciari Romano Sassatelli Giovanni Battista La Sala Obstetrics and Gynecology Unit Department of ObstetricsGynecology and PediatricsAzienda Ospedaliera ASMNIstituto di Ricovero e Cura a Carattere Scientifico42123 Reggio EmiliaItaly Gastroenterology and Digestive Endoscopy Unit Department of Oncology and Advanced TechnologiesAzienda Ospedaliera ASMNIstituto di Ricovero e Cura a Carattere Scientifico42123 Reggio EmiliaItaly Medicine and Gastroenterology Unit Azienda Ospedaliera ASMNIstituto di Ricovero e Cura a Carattere Scientifico42123 Reggio EmiliaItaly Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto University of Modena and Reggio Emilia41124 ModenaItaly

To evaluate the effects of inflammatory bowel diseases(IBDs)on human reproduction,we reviewed the current literature using a systematic search for published studies(articles and/or abstracts)without limits for English *** searched on Medline(through PubMed),the Institute for Scientific Information,the Web of Science and the websites for the registration of controlled trials(http://***/).Bibliographies of retrieved articles,books,expert opinion review articles and reviewed bibliographies from subject experts were manually *** and abstracts were screened initially,and potential relevant articles were identified and *** possible,data were analyzed by comparing IBD patients vs healthy controls,and patients with active IBDs vs those with disease in *** effects of IBDs on female fertility,fertility in infertile couples,pregnancy and male infertility were examined *** with IBDs in remission have normal *** the moment,there is no established guideline for the preservation of fertility in women with IBD undergoing *** data are needed regarding guidelines for the management of these *** regarding IBDs and infertility are currently completely *** the prevalence of intestinal pathology in young adults of childbearing age,this field is of great scientific and clinical interest,opening up important future *** important and as yet unexplored point is the response to treatments for infertility in patients with *** particular,the question is whether the reproductive outcomes(clinical and biological)can be influenced by the IBD of one of the *** goals for successful reproductive outcomes in IBD population are correct counseling and disease *** significantly affect several reproductive aspects of human(female,male,couple)*** data are needed to develop guidelines for the clinical management of subjects of

关键词： Inflammatory bowel diseases Fertility Infertility Pregnancy

Long-term outcome of pancreatic function following oncological surgery in children:Institutional experience and review of the literature

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World Journal of Clinical Cases 2021年第25期9卷 7340-7349页

作者： Giulia Bolasco Teresa Capriati chiara Grimaldi Lidia Monti maria Debora De Pasquale Ippolita Patrizia Patera Marco Spada Giuseppe Maggiore Antonella Diamanti Hepatology Gastroenterology and Nutrition Unit“Bambino Gesù”Children’s HospitalIRCCSRome 00165Italy Division of Hepatobiliopancreatic Surgery Liver and Kidney Transplantation"Bambino Gesù"Children's HospitalIRCCSRome 00165Italy Radiology Department "Bambino Gesù"Children’s HospitalIRCCSRome 00165Italy Hematology/Oncology Department "Bambino Gesu"Children's HospitalIRCCSRome 00165Italy Endocrinology and Diabetes Unit "Bambino Gesù"Children’s HospitalIRCCSRome 00165Italy

BACKGROUND Pancreatic neoplasms are uncommon in children and in most cases they are benign or have low malignant *** and solid pseudopapillary tumor are the most frequent types in early and late childhood,*** resection,although burdened by severe complications,is the only curative treatment for these *** surgery may result in impaired exocrine and endocrine pancreatic ***,limited data are available on the long-term pediatric pancreatic function following surgical *** To investigate endocrine and exocrine pancreatic function and growth after oncological pancreatic surgery in a pediatric *** A retrospective analysis of all pediatric patients who underwent surgery for pancreatic neoplasm in our Institution from January 31,2002 to the present was *** and exocrine insufficiency,auxological and fat-soluble vitamin status(A,D,E and clotting tests)were assessed at diagnosis and at every follow-up *** insufficiency was defined as steatorrhea with fecal elastase-1<200μg/g stool,while endocrine insufficiency was identified as onset of Diabetes or Impaired Glucose *** was evaluated based on body mass index(BMI)z-score *** Sixteen patients(12 girls and 4 boys,mean age 10.7±5.3 years),were *** patients(56%)had a neoplasm in the pancreatic head,4 in the body/tail,2 in the tail and 1 in the *** findings were as follows:Solid pseudopapillary tumor in 10 patients(62.5%),insulinoma in 2 patients,neuroendocrine tumor in 2 patients and acinar cell carcinoma in 2 *** most frequent surgery was pancreaticoduodenectomy(50%).Exocrine failure occurred in 4 patients(25%)and endocrine failure in 2 patients(12.5%).Exocrine insufficiency occurred early(within 6 mo after surgery)and endocrine insufficiency later(8 and 10 years after surgery).Mean BMI z-score was 0.36±1.1 at diagnosis and 0.27±0.95 at the last ***

关键词： Pancreatic neoplasms Pancreatic function Children Malabsorption Pancreatic failure Growth

Private somatic mutations identified with liquid biopsy lead tumor progression in solid cancers

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 718-725页

作者： maria Palmieri Margherita Baldassarri Nicola Iuso Francesca Fava Alessandra Fabbiani Francesco Cetta chiara Fallerini Rossella Tita maria Antonietta Mencarelli Alessandra Renieri Elisa Frullanti Medical Genetics University of SienaSiena 53100Italy Department of Medical Biotechnologies Med Biotech Hub and Competence CenterUniversity of SienaSiena 53100Italy Genetica Medica Azienda Ospedaliera Universitaria SeneseSiena 53100Italy

Aim:Primary tumors can be divided into oncogene-addicted(e.g.,lung)and non-oncogene addicted(e.g.,breast).Only the former group has an Achilles-heel single gene for successful target therapy,whereas the latter has mutations of multiple causative ***,tissue biopsy used for genetic surveys do not give a complete picture of the molecular profile and clonal evolution,but only provide static information over ***:A series of 133 patients with 16 different solid tumors were *** samples were collected and cell-free DNA(cfDNA)was *** libraries were analyzed using AVENIO circulating tumor DNA(ctDNA)Expanded Kit and Illumina NextSeq 550 for sequencing was *** order to evaluate the clinical evolution over time,a second cfDNA analysis was performed after a mean interval of 2 ***:Through the cfDNA liquid biopsy,we found 89 pathogenic variants in 54 ***,lung,and prostate cancers showed the largest number of mutated ***53,PIK3CA,FGFR3,KRAS,and ERBB2 were the most frequently mutated genes among 16 different *** distribution didn’t show any type of *** particular,every patient with disease progression seems to have a“private”combination of gene pair mutations,with TP53 as the most frequently mutated ***:We showed that the clonal evolution of tumors includes a private combination of genes,regardless of tumor *** the future,the cancer treatment can be the targeted therapy against specific tumor mutation(s).The present approach seems promising to both identify key cancer genes and follow clonal evolution over time.

关键词： Cell-free DNA liquid biopsy solid tumors advanced tumors private mutations targeted-therapy

Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis

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World Journal of Gastroenterology 2017年第8期23卷 1458-1468页

作者： Luca Rinaldi Fabio Nascimbeni Mauro Giordano chiara Masetti Barbara Guerrera Annalisa Amelia maria chiara Fascione Stefano Ballestri Dante Romagnoli Rosa Zampino Riccardo Nevola Enrica Baldelli Natalina Iuliano Valerio Rosato Amedeo Lonardo Luigi Elio Adinolfi Internal Medicine Clinical Hospital of MarcianiseSecond University of Naples Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesSecond University of Naples Outpatient Liver Clinic and Internal Medicine NOCSAEBaggiovaraAzienda USLModena Internal Medicine Pavullo HospitalAzienda Sanitaria Locale

To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related *** prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox *** the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class ***

关键词： Liver cirrhosis Hepatocellular carcinoma Metabolic syndrome Nonalcoholic fatty liver disease Cardiovascular diseases

Outcome of endotherapy for pancreas divisum in patients with acute recurrent pancreatitis

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World Journal of Gastroenterology 2014年第46期20卷 17468-17475页

作者： Alberto mariani Milena Di Leo maria chiara Petrone Paolo Giorgio Arcidiacono Antonella Giussani Raffaella Alessia Zuppardo Giulia Martina Cavestro Pier Alberto Testoni Gastroenterology and Gastrointestinal Endoscopy Unit Division of Experimental OncologyIRCCS San Raffaele Scientific Institute - Vita Salute San Raffaele University20132 MilanItaly

AIM: To assess the rate of relapses of acute pancreatitis (AP), recurrent AP (RAP) and the evolution of endosonographic signs of chronic pancreatitis (CP) in patients with pancreas divisum (PDiv) and RAP.

关键词： Endoscopic retrograde cholangiopancreatography Magnetic resonance cholangiopancreatography with secretin stimulation Minor papilla endotherapy Pancreatic stenting Endoscopic ultrasonography

Liver-side of inflammatory bowel diseases:Hepatobiliary and druginduced disorders

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World Journal of Hepatology 2021年第12期13卷 1828-1849页

作者： Stefano Mazza Sara Soro maria chiara Verga Biagio Elvo Francesca Ferretti Fabrizio Cereatti Andrea Drago Roberto Grassia Gastroenterology and Digestive Endoscopy Unit ASST CremonaCremona 26100Italy Gastroenterology Unit ASST Fatebenefratelli-SaccoDepartment of Biomedical and Clinical Sciences(DIBIC)Universitàdegli Studi di MilanoMilan 20157Italy

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases(IBD),both in Crohn’s disease and ulcerative colitis(UC),and therefore represent a diagnostic *** conditions include primary sclerosing cholangitis(PSC)as the main form,variant forms of PSC(namely small-duct PSC,PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis)and granulomatous *** is by far the most common,presenting in up to 8%of IBD patients,more frequently in *** genetic foci have been identified,but environmental factors are preponderant on disease *** course of the two diseases is typically *** diagnosis is based mostly on typical radiological findings and exclusion of secondary *** of cholangiocarcinoma is significantly increased in PSC,as well as the risk of colorectal cancer in patients with PSC and IBD-related *** disease-modifying drugs are approved to ***,PSC management is directed against symptoms and complications and includes medical therapies for pruritus,endoscopic treatment of biliary stenosis and liver transplant for end-stage liver *** nonimmune-mediated hepatobiliary disorders are gallstone disease,whose incidence is higher in IBD and reported in up to one third of IBD patients,non-alcoholic fatty liver disease,pyogenic liver abscess and portal vein *** liver injury(DILI)is an important issue in IBD,since most IBD therapies may cause liver toxicity;however,the incidence of serious adverse events is *** and methotrexate are the most associated with DILI,while the risk related to anti-tumor necrosis factor-αand anti-integrins is *** on hepatotoxicity of newer drugs approved for IBD,like anti-interleukin 12/23 and tofacitinib,are still scarce,but the evidence from other rheumatic diseases is *** B reactivation during immunosuppressive therapy is a major

关键词： Inflammatory bowel diseases Hepatobiliary disorders Primary sclerosing cholangitis Drug-induced liver injury Biological drugs Viral hepatitis

Interpreting Results of Ethanol, Carbamazepine and Topiramate in Putrefied Postmortem Specimens： A Case Report

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Journal of Pharmacy and Pharmacology 2016年第2期4卷 45-51页

作者： maria chiara David Lucia Broccoli Luana Lionetto PhD Forensic Science-Department of Public Healthy Legal Medicine - University of Tor Vergata 00133 Rome Italy PhD Legal Medicine and Forensic Science 00157 Rome ltaly PhD Advanced Molecular Diagnostics Unit (DiMA) IDI-IRCCS Istituto Dermopatico dell 'lmmacolata 00167 Rome Italy

CBZ （carbamazepine）, CBZ-epox （carbamazepine-10,11-epoxide）, TPR （topiramate） and ethanol were detected in 37-year-old woman buried in the wall founded eighteen months after death. The woman was in treatment with anticonvulsants. The cause of death was strangulation investigated by immunohistochemical with GPA （glycophorin A）. Routine analyses for drugs of abuse, therapeutic drugs and volatiles were conducted. Carbamazepine, Topiramate and Alcohol were quantified in abdominal effusion, gastric wall, spleen, douglas fluid, skeletal muscles, endothoracic fluid, kidney, liver, heart and bone marrow. CBZ, CBZ-epox and TPR were recovered in samples deproteinized by acetonitrile spiked with DNSnVal as Internal Standard. Compounds were detected by HPLC-MS/MS. Alcohol was detected in any specimens by HS-GC/FID. CBZ concentrations were ranged from 0.49 in liver to 13.6 ~tg/g in endothoracic fluid; CBZ-Epox 0.46 in skeletal muscle, and 1.13 pg/g in Douglas fluid; TPR 0.11 in gastric wall and 1.23 Ixg/g in endothoracic fluid; alcohol from 0.17 in bone marrow to 0,75 mg/g in Douglas fluid. To our knowledge this is the first report of the presence of carbamazepine, topiramate, and alcohol in post mortem putrefied specimens.

关键词： Carbamazepine topimarate HPLC-MS/MS postmortem putrefied saponified.