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Tumour budding

Eva Karamitopoulou, Martin Wartenberg, Inti Zlobec, Silvia Cibin, Mathias Worni, Beat Gloor, Alessandro Lugli
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with rising incidence. Biomarkers that would help the prognostic stratification of patients are urgently needed. Although tumour budding (BD) is a strong and independent prognostic factor in PDAC, is not included in histopathology reports, partly due to lack of standardized scoring system. AIM: Aim of the present work is to assess the reliability and reproducibility of the BD scoring system recently proposed by the International Tumour Budding Concensus Conference (ITBCC) 2016, in a well-characterized PDAC-cohort (n=120) with complete clinico-pathological and follow-up information...
March 1, 2018: Histopathology
Alhadi Almangush, Ilkka Heikkinen, Nassira Bakhti, Laura K Mäkinen, Joonas H Kauppila, Matti Pukkila, Jaana Hagström, Jussi Laranne, Ylermi Soini, Luiz Paulo Kowalski, Reidar Grénman, Caj Haglund, Antti A Mäkitie, Ricardo D Coletta, Ilmo Leivo, Tuula Salo
AIMS: Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome and there is a need to identify better prognostic factors. Recently, tumour-stroma ratio (TSR) has been associated with prognosis in several cancers. This multi-institutional study evaluates the prognostic value of TSR from original HE-stained tumor-resection slides in a series of early-stage (cT1-2N0) OTSCC patients. METHODS AND RESULTS: A TSR cutoff value of 50% was used to divide the patients into stroma-rich (≥50%) and stroma-poor (<50%) groups...
February 10, 2018: Histopathology
Olivier Zajac, Joel Raingeaud, Fotine Libanje, Celine Lefebvre, Dora Sabino, Isabelle Martins, Pétronille Roy, Clara Benatar, Charlotte Canet-Jourdan, Paula Azorin, Mélanie Polrot, Patrick Gonin, Salima Benbarche, Sylvie Souquere, Gerard Pierron, Damien Nowak, Ludovic Bigot, Michel Ducreux, David Malka, Camille Lobry, Jean-Yves Scoazec, Clarisse Eveno, Marc Pocard, Jean-Luc Perfettini, Dominique Elias, Peggy Dartigues, Diane Goéré, Fanny Jaulin
Metastases account for 90% of cancer-related deaths; thus, it is vital to understand the biology of tumour dissemination. Here, we collected and monitored >50 patient specimens ex vivo to investigate the cell biology of colorectal cancer (CRC) metastatic spread to the peritoneum. This reveals an unpredicted mode of dissemination. Large clusters of cancer epithelial cells displaying a robust outward apical pole, which we termed tumour spheres with inverted polarity (TSIPs), were observed throughout the process of dissemination...
March 2018: Nature Cell Biology
Inti Zlobec, Alessandro Lugli
No abstract text is available yet for this article.
January 29, 2018: Nature Reviews. Cancer
I Ubink, W J van Eden, P Snaebjornsson, N F M Kok, J van Kuik, W M U van Grevenstein, M M Laclé, J Sanders, R J A Fijneman, S G Elias, I H M Borel Rinkes, A G J Aalbers, O Kranenburg
BACKGROUND: Patients with colorectal peritoneal carcinomatosis have a very poor prognosis. The recently developed consensus molecular subtype (CMS) classification of primary colorectal cancer categorizes tumours into four robust subtypes, which could guide subtype-targeted therapy. CMS4, also known as the mesenchymal subtype, has the greatest propensity to form distant metastases. CMS4 status and histopathological features of colorectal peritoneal carcinomatosis were investigated in this study...
January 2018: British Journal of Surgery
Marloes Swets, Peter J K Kuppen, Erik J Blok, Hans Gelderblom, Cornelis J H van de Velde, Iris D Nagtegaal
BACKGROUND: Several histological high-risk factors are used as an indication for adjuvant therapy in stage II colon cancer. Those and other factors, including lymphatic invasion, perineural invasion (PNI), venous invasion and tumour budding are associated with decreased outcome. In this study, we evaluated the prognostic and predictive values of these biomarkers in a cohort of rectal cancer patients. MATERIALS AND METHODS: The trial-based cohort consisted of 221npTNM stage II-III rectal cancer patients, included in the PROCTOR/SCRIPT trial, a multicentre randomised phase III trial...
January 2018: European Journal of Cancer
Rosario Alberto Caruso, Giuseppe Angelico, Eleonora Irato, Rosalba de Sarro, Giovanni Tuccari, Antonio Ieni
Autophagy represents a catabolic process in which cellular protein and organelles are engulfed into autophagosomes, digested in lysosomes and reutilized for the cellular metabolism. In neoplastic conditions, autophagy may act either as a tumour suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumour growth. Although enhanced autophagy has been reported in hypoxic areas of solid tumors, there are only few ultrastructural reports concerning the relationships between autophagy and tumor grade...
January 2018: Ultrastructural Pathology
Alhadi Almangush, Matti Pirinen, Ilkka Heikkinen, Antti A Mäkitie, Tuula Salo, Ilmo Leivo
BACKGROUND: Tumour budding has been reported as a promising prognostic marker in many cancers. This meta-analysis assessed the prognostic value of tumour budding in oral squamous cell carcinoma (OSCC). METHODS: We searched OvidMedline, PubMed, Scopus and Web of Science for articles that studied tumour budding in OSCC. We used reporting recommendations for tumour marker (REMARK) criteria to evaluate the quality of studies eligible for meta-analysis. RESULTS: A total of 16 studies evaluated the prognostic value of tumour budding in OSCC...
February 20, 2018: British Journal of Cancer
Mercedes Tkach, Joanna Kowal, Clotilde Théry
In the past decade, cell-to-cell communication mediated by exosomes has attracted growing attention from biomedical scientists and physicians, leading to several recent publications in top-tier journals. Exosomes are generally defined as secreted membrane vesicles, or extracellular vesicles (EVs), corresponding to the intraluminal vesicles of late endosomal compartments, which are secreted upon fusion of multi-vesicular endosomes with the cell's plasma membrane. Cells, however, were shown to release other types of EVs, for instance, by direct budding off their plasma membrane...
January 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Ryuji Fukuzawa, Matthew R Anaka, Ian M Morison, Anthony E Reeve
Wilms tumour (WT) is an embryonal tumour that recapitulates kidney development. The normal kidney is formed from two distinct embryological origins: the metanephric mesenchyme (MM) and the ureteric bud (UB). It is generally accepted that WT arises from precursor cells in the MM; however whether UB-equivalent structures participate in tumorigenesis is uncertain. To address the question of the involvement of UB, we assessed 55 Wilms tumours for the molecular features of MM and UB using gene expression profiling, immunohistochemsitry and immunofluorescence...
2017: PloS One
Friedrich Prall, Claudia Maletzki, Maja Hühns, Mathias Krohn, Michael Linnebacher
Tumour budding and podia formation are well-appreciated in surgical pathology as an aggressive invasion phenotype of colorectal carcinoma cells that is attained in the microenvironment of the invasive margin. In this study, we addressed how tumour budding and podia formation feature in xenografts. Primary colorectal carcinomas (N = 44) of various molecular types (sporadic standard type, high-degree microsatellite-unstable, CpG island methylator phenotype) were transplanted subcutaneously into T and B cell-deficient NSG mice, making possible immunohistochemistry with routine surgical pathology antibodies...
2017: PloS One
Dermot O'Sullivan, Paul Dowling, Helena Joyce, Edel McAuley, Andrew McCann, Michael Henry, Brianan McGovern, Paul Barham, Fergal C Kelleher, Jean Murphy, Susan Kennedy, Niall Swan, Michael Moriarty, Martin Clynes, Annemarie Larkin
BACKGROUND: Discovery and validation of new antibody tractable targets is critical for the development of new antibody therapeutics to address unmet needs in oncology. METHODS: A highly invasive clonal variant of the MDA-MB-435S cell line was used to generate monoclonal antibodies (MAbs), which were screened for anti-invasive activity against aggressive cancer cells in vitro. The molecular target of selected inhibitory MAb 9E1 was identified using immunoprecipitation/liquid chromatography-tandem mass spectrometry...
October 24, 2017: British Journal of Cancer
Viktor H Koelzer, Naziheh Assarzadegan, Heather Dawson, Bojana Mitrovic, Andrea Grin, David E Messenger, Richard Kirsch, Robert H Riddell, Alessandro Lugli, Inti Zlobec
Tumour budding in colorectal cancer is an important prognostic factor. A recent consensus conference elaborated recommendations and key issues for future studies, among those the use of pan-cytokeratin stains, especially in stage II patients. We report the first prospective diagnostic experience using pan-cytokeratin for tumour budding assessment. Moreover, we evaluate tumour budding using pan-cytokeratin stains and disease-free survival (DFS) in stage II patients. To this end, tumour budding on pan-cytokeratin-stained sections was evaluated by counting the number of tumour buds in 10 high-power fields (0...
July 2017: Journal of Pathology. Clinical Research
Jeong-Hwa Woo, Ji-Hye Ahn, Dae Sik Jang, Kyung-Tae Lee, Jung-Hye Choi
The flower bud of Syzygium aromaticum (clove) has been used for centuries as a spice and herbal medicine. The biological activities of kumatakenin, a flavonoid that has recently been isolated from cloves, are poorly characterized. In the present study, the anticancer effects of kumatakenin in human ovarian cancer cells and tumor-associated macrophages (TAMs) were investigated. We found that kumatakenin exhibited significant cytotoxic activity in human ovarian cancer cells, SKOV3 and A2780. A propidium iodide and Annexin V-FITC staining assay showed that kumatakenin induces apoptosis in ovarian cancer cells...
September 13, 2017: Journal of Agricultural and Food Chemistry
Peter Kubatka, Sona Uramova, Martin Kello, Karol Kajo, Peter Kruzliak, Jan Mojzis, Desanka Vybohova, Marian Adamkov, Karina Jasek, Zora Lasabova, Pavol Zubor, Silvia Fialova, Svetlana Dokupilova, Peter Solar, Martin Pec, Katarina Adamicova, Jan Danko, Mariusz Adamek, Dietrich Busselberg
It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF-7 cells was carried out...
November 2017: Journal of Cellular and Molecular Medicine
J H Park, H van Wyk, C S D Roxburgh, P G Horgan, J Edwards, D C McMillan
BACKGROUND: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. METHODS: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR)...
May 23, 2017: British Journal of Cancer
Antonia K Roseweir, Pamela McCall, Alison Scott, Benjamin Liew, Zhi Lim, Elizabeth A Mallon, Joanne Edwards
1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry...
June 6, 2017: Oncotarget
Tarig Magdeldin, Víctor López-Dávila, Judith Pape, Grant W W Cameron, Mark Emberton, Marilena Loizidou, Umber Cheema
The hallmark of tumours is the ability of cancerous cells to promote vascular growth, to disseminate and invade to distant organs. The metastatic process is heavily influenced by the extracellular matrix (ECM) density and composition of the surrounding tumour microenvironment. These microenvironmental cues, which include hypoxia, also regulate the angiogenic processes within a tumour, facilitating the spread of cancer cells. We engineered compartmentalized biomimetic colorectal tumouroids with stromal surrounds that comprised a range of ECM densities, composition and stromal cell populations...
March 9, 2017: Scientific Reports
Gregor Rieger, Viktor H Koelzer, Heather E Dawson, Martin D Berger, Marion Hädrich, Daniel Inderbitzin, Alessandro Lugli, Inti Zlobec
AIMS: Tumour budding in colorectal cancer (CRC) is a recognized prognostic parameter. The aim of this study was to address the use of cytokeratin immunostaining for the visualization and scoring of tumour buds. METHODS AND RESULTS: Ten hotspots (0.238 mm(2) ) of peritumoural budding (PTB) and intratumoural budding (ITB) were evaluated in surgical resections from 215 patients. The budding counts in the 10 densest regions anywhere in the tumour were combined into an overall tumour budding (OTB) score...
January 6, 2017: Histopathology
Zarin Nuzhat, Vyjayanthi Kinhal, Shayna Sharma, Gregory E Rice, Virendra Joshi, Carlos Salomon
Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer...
March 7, 2017: Oncotarget
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