Full Text Journal Articles by
Author Inti Zlobec

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Tumour budding and its clinical implications in gastrointestinal cancers.

Inti Zlobec, Martin D Berger, Alessandro Lugli,

Tumour budding in colorectal cancer has become an important prognostic factor. Represented by single cells or small tumour cell clusters at the invasion front of the tumour mass, these tumour buds seem to reflect cells in a 'hybrid' state of epithelial-mesenchymal transition, and evidence indicates that the presence of these ... Read more >>

Br. J. Cancer (British Journal of Cancer)
[2020, :]

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Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

Caroline Contat, Pierre-Benoit Ancey, Nadine Zangger, Silvia Sabatino, Justine Pascual, Stéphane Escrig, Louise Jensen, Christine Goepfert, Bernard Lanz, Mario Lepore, Rolf Gruetter, Anouk Rossier, Sabina Berezowska, Christina Neppl, Inti Zlobec, Stéphanie Clerc-Rosset, Graham William Knott, Jeffrey C Rathmell, E Dale Abel, Anders Meibom, Etienne Meylan,

Glucose utilization increases in tumors, a metabolic process that is observed clinically by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one ... Read more >>

Elife (eLife)
[2020, 9:]

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Editorial: Computational Pathology.

Behzad Bozorgtabar, Dwarikanath Mahapatra, Inti Zlobec, Tilman T Rau, Jean-Philippe Thiran,

Front Med (Lausanne) (Frontiers in Medicine)
[2020, 7:245]

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Are tumour grade and tumour budding equivalent in colorectal cancer? A retrospective analysis of 771 patients.

Inti Zlobec, Heather E Dawson, Annika Blank, John-Melle Bokhorst, Martin D Berger, Iris D Nagtegaal, Alessandro Lugli,

BACKGROUND:Tumour grade is traditionally considered in the management of patients with colorectal cancer. However, a large body of literature suggests that a related feature, namely tumour budding, may have a more important clinical impact. The aim of our study is to determine the correlation between tumour grade and tumour budding ... Read more >>

Eur. J. Cancer (European journal of cancer (Oxford, England : 1990))
[2020, 130:139-145]

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Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score.

Heather Dawson, Lucine Christe, Micha Eichmann, Stefan Reinhard, Inti Zlobec, Annika Blank, Alessandro Lugli,

AIMS:The tumour-node-metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, ... Read more >>

Histopathology (Histopathology)
[2020, 76(4):572-580]

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Current opinion, status and future development of digital pathology in Switzerland.

Julia Unternaehrer, Rainer Grobholz, Andrew Janowczyk, Inti Zlobec, ,

AIMS:The transition from analogue to digital pathology (DP) is underway in Switzerland. To assess relevant experiences of pathologists with DP and gauge their outlook towards a digital future, a national survey was conducted by the Swiss Digital Pathology Consortium. Similar surveys were conducted in other countries, enabling a meta-analysis of ... Read more >>

J. Clin. Pathol. (Journal of clinical pathology)
[2020, 73(6):341-346]

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A Digital Pathology-Based Shotgun-Proteomics Approach to Biomarker Discovery in Colorectal Cancer.

Stefan Zahnd, Sophie Braga-Lagache, Natasha Buchs, Alessandro Lugli, Heather Dawson, Manfred Heller, Inti Zlobec,

Background:Biomarkers in colorectal cancer are scarce, especially for patients with Stage 2 disease. The aim of our study was to identify potential prognostic biomarkers from colorectal cancers using a novel combination of approaches, whereby digital pathology is coupled to shotgun proteomics followed by validation of candidates by immunohistochemistry (IHC) using ... Read more >>

J Pathol Inform (Journal of pathology informatics)
[2019, 10:40]

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ATG12 deficiency leads to tumor cell oncosis owing to diminished mitochondrial biogenesis and reduced cellular bioenergetics.

He Liu, Zhaoyue He, Nina Germič, Hyrijie Ademi, Živa Frangež, Andrea Felser, Shuang Peng, Carsten Riether, Valentin Djonov, Jean-Marc Nuoffer, Cédric Bovet, Irena Mlinarič-Raščan, Inti Zlobec, Martin Fiedler, Aurel Perren, Hans-Uwe Simon,

In contrast to the "Warburg effect" or aerobic glycolysis earlier generalized as a phenomenon in cancer cells, more and more recent evidence indicates that functional mitochondria are pivotal for ensuring the energy supply of cancer cells. Here, we report that cancer cells with reduced autophagy-related protein 12 (ATG12) expression undergo ... Read more >>

Cell Death Differ. (Cell death and differentiation)
[2020, 27(6):1965-1980]

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Validation of the International Tumor Budding Consensus Conference (ITBCC) 2016 recommendation in squamous cell carcinoma of the lung-a single-center analysis of 354 cases.

Christina Neppl, Inti Zlobec, Ralph A Schmid, Sabina Berezowska,

There are no universally accepted grading systems in pulmonary squamous cell carcinoma (pSQCC). Recently, tumor budding, cell nest size, and spread through airspaces (STAS) have been proposed as grading scheme candidates. Tumor budding is a well-established independent prognostic factor in colorectal cancer. The International Tumor Budding Consensus Conference (ITBCC) provided ... Read more >>

Mod. Pathol. (Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc)
[2020, 33(5):802-811]

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Evaluation of Tumor Budding in Primary Colorectal Cancer and Corresponding Liver Metastases Based on H&E and Pancytokeratin Staining.

Annika Blank, Carla Schenker, Heather Dawson, Guido Beldi, Inti Zlobec, Alessandro Lugli,

In colorectal cancer, tumor budding is associated with tumor progression and represents an additional prognostic factor in the TNM classification. Tumor buds can be found at the invasive front (peritumoral budding; PTB) and in the tumor center (intratumoral budding; ITB) of primary tumors. Previous studies have shown that tumor buds ... Read more >>

Front Med (Lausanne) (Frontiers in medicine)
[2019, 6:247]

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Oncologic long-term outcomes of emergency versus elective resection for colorectal cancer.

Joël L Lavanchy, Lukas Vaisnora, Tobias Haltmeier, Inti Zlobec, Lukas E Brügger, Daniel Candinas, Beat Schnüriger,

PURPOSE:Long-term outcomes in patients undergoing emergency versus elective resection for colorectal cancer (CRC) are discussed controversially. This study aims to assess long-term outcomes of emergency versus elective CRC surgery. METHODS:Single-center retrospective cohort study. Patients undergoing emergency or elective CRC surgery from July 2002 to January 2013 were included. Primary outcome ... Read more >>

Int J Colorectal Dis (International journal of colorectal disease)
[2019, 34(12):2091-2099]

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Synaptic proximity enables NMDAR signalling to promote brain metastasis.

Qiqun Zeng, Iacovos P Michael, Peng Zhang, Sadegh Saghafinia, Graham Knott, Wei Jiao, Brian D McCabe, José A Galván, Hugh P C Robinson, Inti Zlobec, Giovanni Ciriello, Douglas Hanahan,

Metastasis-the disseminated growth of tumours in distant organs-underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying frequencies in all cancer subtypes. Previous studies revealed parameters of breast cancer metastasis to the ... Read more >>

Nature (Nature)
[2019, 573(7775):526-531]

Cited: 1 time

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Comparison of the 7th and 8th Edition of the UICC/AJCC TNM Staging System in Primary Resected Squamous Cell Carcinomas of the Lung-A Single Center Analysis of 354 Cases.

Christina Neppl, Manuel D Keller, Amina Scherz, Patrick Dorn, Ralph A Schmid, Inti Zlobec, Sabina Berezowska,

Background: The AJCC/UICC TNM (tumor, node, metastasis) classification is a standardized system for the description of anatomical extent and stage grouping of solid malignant tumors and is regularly updated. We aimed at testing the new 2017 8th edition of the TNM classification (TNM8) compared to the former 2009 7th edition ... Read more >>

Front Med (Lausanne) (Frontiers in medicine)
[2019, 6:196]

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TRPM4 is highly expressed in human colorectal tumor buds and contributes to proliferation, cell cycle, and invasion of colorectal cancer cells.

Sven Kappel, Paulina Stokłosa, Barbara Hauert, Daniela Ross-Kaschitza, Anna Borgström, Roland Baur, José A Galván, Inti Zlobec, Christine Peinelt,

Transient receptor potential melastatin-4 channel (TRPM4) dysregulation contributes to heart conditions, immune diseases, and cervical and prostate cancer. Up to now, the involvement of TRPM4 in colorectal cancer (CRC) pathophysiology remains unknown. Here, we investigated tumor tissue microarrays from 379 CRC patients and analyzed TRPM4 protein expression, tumor characteristics, and clinical ... Read more >>

Mol Oncol (Molecular oncology)
[2019, 13(11):2393-2405]

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Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front

Christian Schürch, Salil Bhate, Graham Barlow, Darci Phillips, Luca Noti, Inti Zlobec, Pauline Chu, Sarah Black, Janos Demeter, David McIlwain, Nikolay Samusik, Yury Goltsev, Garry Nolan,

SUMMARY Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We optimized CO-Detection by indEXing (CODEX) for para ffin-em bedded tissue microarrays, enabling profiling of 140 tissue regions from 35 advanced-stage ... Read more >>

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Cell Line Derived Xenograft Mouse Models Are a Suitable in vivo Model for Studying Tumor Budding in Colorectal Cancer.

Laurent M C Georges, Olivier De Wever, José A Galván, Heather Dawson, Alessandro Lugli, Pieter Demetter, Inti Zlobec,

Tumor budding (TB) is an important prognostic parameter in colorectal cancer (CRC) and associated with metastasis. However, the mechanisms of TB have not been fully elucidated and a major limitation is the absence of in vivo models. Here, we determine the suitability of human cell line derived xenografts (CDX) as ... Read more >>

Front Med (Lausanne) (Frontiers in medicine)
[2019, 6:139]

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The IL-33/ST2 pathway shapes the regulatory T cell phenotype to promote intestinal cancer.

Eva Pastille, Marie-Hélène Wasmer, Alexandra Adamczyk, Vivian P Vu, Lukas F Mager, Nhi Ngo Thi Phuong, Vittoria Palmieri, Cedric Simillion, Wiebke Hansen, Stefan Kasper, Martin Schuler, Beat Muggli, Kathy D McCoy, Jan Buer, Inti Zlobec, Astrid M Westendorf, Philippe Krebs,

The composition of immune infiltrates strongly affects the prognosis of patients with colorectal cancer (CRC). Interleukin (IL)-33 and regulatory T cells (Tregs) in the tumor microenvironment have been separately implicated in CRC; however their contribution to intestinal carcinogenesis is still controversial. Here, we reveal that IL-33 signaling promotes CRC by ... Read more >>

Mucosal Immunol (Mucosal immunology)
[2019, 12(4):990-1003]

Cited: 1 time

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Co-expression of cytokeratin and vimentin in colorectal cancer highlights a subset of tumor buds and an atypical cancer-associated stroma.

Sara N Meyer, José A Galván, Stefan Zahnd, Lena Sokol, Heather Dawson, Alessandro Lugli, Inti Zlobec,

Tumor buds in colorectal cancer are hypothesized to undergo a (partial) epithelial-mesenchymal transition (EMT). If so, cytokeratin (CK) and vimentin (VIM) co-expression is expected. CK+/VIM+ can also be found in some stromal cells; however, their origin remains unclear. Here, we determine the frequency of CK+/VIM+ tumor cells and characterize the ... Read more >>

Hum. Pathol. (Human pathology)
[2019, 87:18-27]

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Tumour budding is associated with the mesenchymal colon cancer subtype and RAS/RAF mutations: a study of 1320 colorectal cancers with Consensus Molecular Subgroup (CMS) data.

Anne Trinh, Claudia Lädrach, Heather E Dawson, Sanne Ten Hoorn, Peter J K Kuppen, Marlies S Reimers, Miriam Koopman, Cornelis J A Punt, Alessandro Lugli, Louis Vermeulen, Inti Zlobec,

BACKGROUND:Tumour budding is an important prognostic factor in colorectal cancer (CRC). Molecular profiling of tumour buds suggests (partial) epithelial-mesenchymal transition and cancer stem-cell phenotype, similarly described in the "mesenchymal" Consensus Molecular Subtype 4 (CMS4), which identifies a particularly poor prognostic subgroup. Here, we determine the association of tumour budding with ... Read more >>

Br. J. Cancer (British journal of cancer)
[2018, 119(10):1244-1251]

Cited: 3 times

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Validation of the International Tumor Budding Consensus Conference 2016 recommendations on tumor budding in stage I-IV colorectal cancer.

Heather Dawson, Francesca Galuppini, Peter Träger, Martin D Berger, Peter Studer, Lukas Brügger, Inti Zlobec, Daniel Inderbitzin, Alessandro Lugli,

Tumor budding is a robust prognostic parameter in colorectal cancer and can be used as an additional factor to guide patient management. Although backed by large bodies of data, a standardized scoring method is essential for integrating tumor budding in reporting protocols. The International Tumor Budding Consensus Conference (ITBCC) 2016 ... Read more >>

Hum. Pathol. (Human pathology)
[2019, 85:145-151]

Cited: 2 times

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Stromal PD-1/PD-L1 Expression Predicts Outcome in Colon Cancer Patients.

Jacqueline Wyss, Bastian Dislich, Viktor H Koelzer, José A Galván, Heather Dawson, Marion Hädrich, Daniel Inderbitzin, Alessandro Lugli, Inti Zlobec, Martin D Berger,

INTRODUCTION:The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in controlling immune suppression by down-regulating T effector cell activities, enabling tumor cells to escape from the host's antitumor immunsurveillance. While only a small part of colon cancer cells express PD-L1, we sought to ... Read more >>

Clin Colorectal Cancer (Clinical colorectal cancer)
[2019, 18(1):e20-e38]

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CDX2 in colorectal cancer is an independent prognostic factor and regulated by promoter methylation and histone deacetylation in tumors of the serrated pathway.

Janina Graule, Kristin Uth, Elia Fischer, Irene Centeno, José A Galván, Micha Eichmann, Tilman T Rau, Rupert Langer, Heather Dawson, Ulrich Nitsche, Peter Traeger, Martin D Berger, Beat Schnüriger, Marion Hädrich, Peter Studer, Daniel Inderbitzin, Alessandro Lugli, Mario P Tschan, Inti Zlobec,

BACKGROUND:In colorectal cancer, CDX2 expression is lost in approximately 20% of cases and associated with poor outcome. Here, we aim to validate the clinical impact of CDX2 and investigate the role of promoter methylation and histone deacetylation in CDX2 repression and restoration. METHODS:CDX2 immunohistochemistry was performed on multi-punch tissue microarrays ... Read more >>

Clin Epigenetics (Clinical epigenetics)
[2018, 10(1):120]

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Tumor Heterogeneity in Primary Colorectal Cancer and Corresponding Metastases. Does the Apple Fall Far From the Tree?

Annika Blank, Daniel Edward Roberts, Heather Dawson, Inti Zlobec, Alessandro Lugli,

Colorectal cancer harbors tremendous heterogeneity, with temporal and spatial differences in genetic mutations, epigenetic regulation, and tumor microenvironment. Analyzing the distribution and frequency of genetic, epigenetic, and microenvironment differences within a given tumor and between different sites of a metastatic tumor has been used as a powerful tool to investigate ... Read more >>

Front Med (Lausanne) (Frontiers in medicine)
[2018, 5:234]

Cited: 4 times

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International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study.

Franck Pagès, Bernhard Mlecnik, Florence Marliot, Gabriela Bindea, Fang-Shu Ou, Carlo Bifulco, Alessandro Lugli, Inti Zlobec, Tilman T Rau, Martin D Berger, Iris D Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Y Wang, Prashant Bavi, Michael H A Roehrl, Pamela S Ohashi, Linh T Nguyen, SeongJun Han, Heather L MacGregor, Sara Hafezi-Bakhtiari, Bradly G Wouters, Giuseppe V Masucci, Emilia K Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Mihaela Angelova, Angela Vasaturo, Pauline Maby, Sarah E Church, Helen K Angell, Lucie Lafontaine, Daniela Bruni, Carine El Sissy, Nacilla Haicheur, Amos Kirilovsky, Anne Berger, Christine Lagorce, Jeffrey P Meyers, Christopher Paustian, Zipei Feng, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn van de Water, Shannon van Lent-van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Kyogo Itoh, Prabhu S Patel, Hemangini H Vora, Birva Shah, Jayendrakumar B Patel, Kruti N Rajvik, Shashank J Pandya, Shilin N Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M Marincola, Paolo A Ascierto, Daniel J Sargent, Bernard A Fox, Jérôme Galon,

BACKGROUND:The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with ... Read more >>

Lancet (Lancet (London, England))
[2018, 391(10135):2128-2139]

Cited: 124 times

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GKAP Acts as a Genetic Modulator of NMDAR Signaling to Govern Invasive Tumor Growth.

Leanne Li, Qiqun Zeng, Arjun Bhutkar, José A Galván, Eva Karamitopoulou, Daan Noordermeer, Mei-Wen Peng, Alessandra Piersigilli, Aurel Perren, Inti Zlobec, Hugh Robinson, M Luisa Iruela-Arispe, Douglas Hanahan,

Genetic linkage analysis previously suggested that GKAP, a scaffold protein of the N-methyl-D-aspartate receptor (NMDAR), was a potential modifier of invasion in a mouse model of pancreatic neuroendocrine tumor (PanNET). Here, we establish that GKAP governs invasive growth and treatment response to NMDAR inhibitors of PanNET via its pivotal role in ... Read more >>

Cancer Cell (Cancer cell)
[2018, 33(4):736-751.e5]

Cited: 3 times

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