Luigi Terracciano

Bio: Luigi Terracciano is an academic researcher from University Hospital of Basel. The author has contributed to research in topics: Cancer & Tissue microarray. The author has an hindex of 85, co-authored 555 publications receiving 28574 citations. Previous affiliations of Luigi Terracciano include University of Molise & Humanitas University.

Interferon signaling and treatment outcome in chronic hepatitis C

Abstract: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFNalpha) and ribavirin. It achieves a sustained viral clearance in only 50-60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFNalpha. In patients with a rapid virological response to treatment, pegIFNalpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFNalpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.

Increased MET Gene Copy Number Negatively Affects Survival of Surgically Resected Non–Small-Cell Lung Cancer Patients

Abstract: Purpose To investigate the prognostic role of genomic gain for MET and epidermal growth factor receptor (EGFR) genes in surgically resected non‐small-cell lung cancer (NSCLC).

PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients.

Abstract: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC. We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive. PD-1 positive (+) was significantly associated with current smoking status (P=0.02) and with the presence of KRAS mutations (P=0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology (P=0.005) and with presence of EGFR mutations (P=0.001). In patients treated with EGFR tyrosine kinase inhibitors (N=95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P=0.01) time to progression (TTP: P<0.0001) and survival (OS: P=0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative (P=0.01). PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines.

Abstract: Alessandro Fiocchi, MD, Pediatric Division, Department of Child and Maternal Medicine, University of Milan Medical School at the Melloni Hospital, Milan 20129, Italy. Holger Schünemann, MD, Department of Clinical Epidemiology & Biostatistics, McMaster University Health Sciences Centre, 1200 Main Street West Hamilton, ON L8N 3Z5, Canada. Sami L. Bahna, MD, Pediatrics & Medicine, Allergy & Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130. Andrea Von Berg, MD, Research Institute, Children s department , Marien-Hospital, Wesel, Germany. Kirsten Beyer, MD, Charité Klinik für Pädiatrie m.S. Pneumologie und Immunologie, Augustenburger Platz 1, D-13353 Berlin, Germany. Martin Bozzola, MD, Department of Pediatrics, British Hospital-Perdriel 74-CABA-Buenos Aires, Argentina. Julia Bradsher, PhD, Food Allergy & Anaphylaxis Network, 11781 Lee Jackson Highway, Suite 160, Fairfax, VA 22033. Jan Brozek, MD, Department of Clinical Epidemiology & Biostatistics, McMaster University Health Sciences Centre, 1200 Main Street West Hamilton, ON L8N 3Z5, Canada. Enrico Compalati, MD, Allergy & Respiratory Diseases Clinic, Department of Internal Medicine. University of Genoa, 16132, Genoa, Italy. Motohiro Ebisawa, MD, Department of Allergy, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Kanagawa 228-8522, Japan. Maria Antonieta Guzman, MD, Immunology and Allergy Division, Clinical Hospital University of Chile, Santiago, Chile. Santos Dumont 999. Haiqi Li, MD, Professor of Pediatric Division, Department of Primary Child Care, Children’s Hospital, Chongqing Medical University, China, 400014. Ralf G. Heine, MD, FRACP, Department of Allergy & Immunology, Royal Children’s Hospital, University of Melbourne, Murdoch Children’s Research Institute, Melbourne, Australia. Paul Keith, MD, Allergy and Clinical Immunology Division, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Gideon Lack, MD, King’s College London, Asthma-UK Centre in Allergic Mechanisms of Asthma, Department of Pediatric Allergy, St Thomas’ Hospital, London SE1 7EH, United Kingdom. Massimo Landi, MD, National Pediatric Healthcare System, Italian Federation of Pediatric Medicine, Territorial Pediatric Primary Care Group, Turin, Italy. Alberto Martelli, MD, Pediatric Division, Department of Child and Maternal Medicine, University of Milan Medical School at the Melloni Hospital, Milan 20129, Italy. Fabienne Rancé, MD, Allergologie, Hôpital des Enfants, Pôle Médicochirurgical de Pédiatrie, 330 av. de Grande Bretagne, TSA 70034, 31059 Toulouse CEDEX, France. Hugh Sampson, MD, Jaffe Food Allergy Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, NY 10029-6574. Airton Stein, MD, Conceicao Hospital, Porto Alegre, Brazil. Luigi Terracciano, MD, Pediatric Division, Department of Child and Maternal Medicine, University of Milan Medical School at the Melloni Hospital, Milan 20129, Italy. Stefan Vieths, MD, Division of Allergology, Paul-EhrlichInstitut, Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Str. 51-59, D-63225 Langen, Germany.

AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update

Abstract: Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/ Documents/Bookmarked%20Practice%20Guidelines/ HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations.

Microenvironmental regulation of tumor progression and metastasis.

Abstract: Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.

Pembrolizumab for the treatment of non-small cell lung cancer

Abstract: BackgroundWe assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non–small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. MethodsWe assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. ResultsCommon side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all ...