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https://www.readbyqxmd.com/read/29754823/pol%C3%AE%C2%B5-instability-drives-replication-stress-abnormal-development-and-tumorigenesis
#1
Roberto Bellelli, Valerie Borel, Clare Logan, Jennifer Svendsen, Danielle E Cox, Emma Nye, Kay Metcalfe, Susan M O'Connell, Gordon Stamp, Helen R Flynn, Ambrosius P Snijders, François Lassailly, Andrew Jackson, Simon J Boulton
DNA polymerase ε (POLE) is a four-subunit complex and the major leading strand polymerase in eukaryotes. Budding yeast orthologs of POLE3 and POLE4 promote Polε processivity in vitro but are dispensable for viability in vivo. Here, we report that POLE4 deficiency in mice destabilizes the entire Polε complex, leading to embryonic lethality in inbred strains and extensive developmental abnormalities, leukopenia, and tumor predisposition in outbred strains. Comparable phenotypes of growth retardation and immunodeficiency are also observed in human patients harboring destabilizing mutations in POLE1...
May 3, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29743547/the-protease-activated-receptor2-promotes-rab5a-mediated-generation-of-pro-metastatic-microvesicles
#2
Kaushik Das, Ramesh Prasad, Sreetama Roy, Ashis Mukherjee, Prosenjit Sen
Metastasis, the hallmark of cancer propagation is attributed by the modification of phenotypic/functional behavior of cells to break attachment and migrate to distant body parts. Cancer cell-secreted microvesicles (MVs) contribute immensely in disease propagation. These nano-vesicles, generated from plasma membrane outward budding are taken up by nearby healthy cells thereby inducing phenotypic alterations in those recipient cells. Protease activated receptor 2 (PAR2), activated by trypsin, also contributes to cancer progression by increasing metastasis, angiogenesis etc...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29731961/macrophages-induce-budding-in-aggressive-human-colon-cancer-subtypes-by-protease-mediated-disruption-of-tight-junctions
#3
Kari Trumpi, Nicola Frenkel, Timo Peters, Nicoline M Korthagen, Jennifer M J Jongen, Daniëlle Raats, Helma van Grevenstein, Yara Backes, Leon M Moons, Miangela M Lacle, Jan Koster, Danny Zwijnenburg, Inne H M Borel Rinkes, Onno Kranenburg
Primary human colorectal tumors with a high stromal content have an increased capacity to metastasize. Cancer-associated fibroblasts (CAFs) promote metastasis, but the contribution of other stromal cell types is unclear. Here we searched for additional stromal cell types that contribute to aggressive tumor cell behavior. By making use of the 'immunome compendium'-a collection of gene signatures reflecting the presence of specific immune cell-types-we show that macrophage signatures are most strongly associated with a high CAF content and with poor prognosis in multiple large cohorts of primary tumors and liver metastases...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29708625/role-of-the-wilms-tumor-suppressor-gene-wt1-in-pancreatic-development
#4
Laura Ariza, Ana Cañete, Anabel Rojas, Ramón Muñoz-Chápuli, Rita Carmona
The Wilms tumor suppressor gene (Wt1) encodes a transcription factor involved in the development of a number of organs, but the role played by Wt1 in pancreatic development is unknown. The pancreas contains a population of pancreatic stellate cells (PSC) very important for pancreatic physiology. We described elsewhere that hepatic stellate cells originate from the WT1-expressing liver mesothelium. Thus, we checked if the origin of PSCs was similar. WT1 is expressed in the pancreatic mesothelium. Between E10...
April 30, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29706133/intestinal-paracoccidioidomycosis-resembling-crohn-s-disease-in-a-teenager-a-case-report
#5
Elizete Aparecida Lomazi, Leandro Minatel Vidal de Negreiros, Pedro Vitor Veiga Silva Magalhães, Raquel de Castro Siqueira Togni, Nielce Maria de Paiva, Antonio Fernando Ribeiro, Raquel Franco Leal
BACKGROUND: Differential diagnosis of inflammatory bowel disease is often very challenging. Paracoccidioidomycosis is a fungal disease that can mimic manifestations of Crohn's disease. CASE PRESENTATION: We report a case of a 13-year-old Caucasian boy with abdominal pain for 1.5 years associated with nausea, diarrhea, and weight loss of 10 kg. He presented increased C-reactive protein and an increased erythrocyte sedimentation rate. A colonoscopy showed deep serpiginous ulcers throughout his entire colon and rectum, which suggested Crohn's disease...
April 30, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29705331/disparate-levels-of-beta-catenin-activity-determine-nephron-progenitor-cell-fate
#6
Harini Ramalingam, Alicia R Fessler, Amrita Das, M Todd Valerius, Jeannine Basta, Lynn Robbins, Aaron C Brown, Leif Oxburgh, Andrew P McMahon, Michael Rauchman, Thomas J Carroll
Formation of a functional kidney depends on the balance between renewal and differentiation of nephron progenitors. Failure to sustain this balance can lead to kidney failure or stem cell tumors. For nearly 60 years, we have known that signals from an epithelial structure known as the ureteric bud were essential for maintaining this balance. More recently it was discovered that one molecule, Wnt9b, was necessary for both renewal and differentiation of the nephron progenitor cells. How one ligand signaling through one transcription factor promoted two seemingly contradictory cellular processes was unclear...
April 26, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29700912/coexistence-of-macc1-and-nm23-h1-dysregulation-and-tumor-budding-promise-early-prognostic-evidence-for-recurrence-risk-of-early-stage-colon-cancer
#7
Ersin Ozturk, Secil Ak Aksoy, Nesrin Ugras, Berrin Tunca, Serkan Ceylan, Gulcin Tezcan, Tuncay Yilmazlar, Omer Yerci, Unal Egeli, Gulsah Cecener
The tumor-node-metastasis (TNM) classification, the presence of a mucinous component, and signet ring cells are well-known criteria for identifying patients at a high risk for recurrence and determining the therapeutic approach for early-stage colon cancer (eCC). Nevertheless, recurrence can unexpectedly occur in some eCC cases after surgical resection. The aims of the present study were to evaluate the relation of dysregulated MACC1, c-MET, and NM23-H1 expression with the histopathological features of tumors in recurrence formation in eCC cases...
February 2018: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/29687293/psychosocial-stress-exposure-disrupts-mammary-gland-development
#8
Marianna B Johnson, Joscelyn N Hoffmann, Hannah M You, Ricardo R Lastra, Sully Fernandez, Jordan W Strober, Ahmad B Allaw, Matthew J Brady, Suzanne D Conzen, Martha K McClintock
Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8-25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats...
April 23, 2018: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/29672550/tumor-budding-is-an-independent-prognostic-marker-in-early-stage-oral-squamous-cell-carcinoma-with-special-reference-to-the-mode-of-invasion-and-worst-pattern-of-invasion
#9
Shota Shimizu, Akihiro Miyazaki, Tomoko Sonoda, Kazushige Koike, Kazuhiro Ogi, Jun-Ichi Kobayashi, Takeshi Kaneko, Tomohiro Igarashi, Megumi Ueda, Hironari Dehari, Akira Miyakawa, Tadashi Hasegawa, Hiroyoshi Hiratsuka
Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding...
2018: PloS One
https://www.readbyqxmd.com/read/29663884/advances-in-tumor-targeted-liposomes
#10
A Jain, S K Jain
Cancer remains a deadly disease for effective treatment. Although anomalous tumor microenvironment is now widely exploited for targeted chemotherapy, safe and efficacious drug delivery to tumor cells is not still warranted. Liposomes are promising biodegradable and biocompatible nanocarriers having potential amenability for surface and internal modifications, and extraordinary capability to carry both hydrophilic as well as hydrophobhic drugs. Meticulous fabrication of liposomes with tumor selective ligand(s) and PEGylation reduces immunogenicity and increase target-specificity...
April 15, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#11
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29658680/rectal-cancer-and-the-pathologist
#12
Mariana Berho, Pablo A Bejarano
INTRODUCTION: Examination of the rectum by pathologists is instrumental in the management of patients affected by rectal carcinoma. That role includes evaluation of multiple gross and microscopic features that convey prognostic implications. EVIDENCE ACQUISITION: The analysis is based on the authors' experience handling rectal specimens along with review of the pertinent literature in these areas: margins of excision, quality of the mesorectum, diligence and techniques to sample lymph nodes, tumor budding, grading of residual amount of carcinoma after pre-operative therapy, vascular/perineural invasion, and staging the tumor...
April 13, 2018: Minerva Chirurgica
https://www.readbyqxmd.com/read/29626253/interobserver-variability-in-the-h-e-based-assessment-of-tumor-budding-in-pt3-4-colon-cancer-does-it-affect-the-prognostic-relevance
#13
Benedikt Martin, Eva Schäfer, Elzbieta Jakubowicz, Patrick Mayr, Regina Ihringer, Matthias Anthuber, Gerhard Schenkirsch, Tina Schaller, Bruno Märkl
Tumor budding is a mostly accepted adverse prognostic factor in colorectal carcinoma. It is on the cusp of a widespread use after agreement was reached recently on uniform assessment criteria. We investigated whether the interobserver variability has a direct influence on the prognostic relevance in pT3/4 colon cancer in the background of different levels of experience of the investigators. In total, six investigators with different levels of experience evaluated tumor budding on H&E slides in 244 cases with primary diagnosed (2002-2011) colon carcinoma (pT3/4, N+/-, M0)...
April 6, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29624511/poorly-differentiated-clusters-predict-colon-cancer-recurrence-an-in-depth-comparative-analysis-of-invasive-front-prognostic-markers
#14
Tsuyoshi Konishi, Yoshifumi Shimada, Lik Hang Lee, Marcela S Cavalcanti, Meier Hsu, Jesse Joshua Smith, Garrett M Nash, Larissa K Temple, José G Guillem, Philip B Paty, Julio Garcia-Aguilar, Efsevia Vakiani, Mithat Gonen, Jinru Shia, Martin R Weiser
This study aimed to compare common histologic markers at the invasive front of colon adenocarcinoma in terms of prognostic accuracy and interobserver agreement. Consecutive patients who underwent curative resection for stages I to III colon adenocarcinoma at a single institution in 2007 to 2014 were identified. Poorly differentiated clusters (PDCs), tumor budding, perineural invasion, desmoplastic reaction, and Crohn-like lymphoid reaction at the invasive front, as well as the World Health Organization (WHO) grade of the entire tumor, were analyzed...
April 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29610361/subcutaneous-injection-of-pluripotent-stem-cells-in-mice
#15
Kristina Vintersten Nagy, Andras Nagy
This protocol describes the production of teratomas and teratocarcinomas used to determine the in vivo developmental potential of adult or embryonic tissues, including early-stage embryos, somites, and tail bud, as well as embryonic and other pluripotent stem cells. Resulting tumors are screened by histology and markers to assess differentiation of the tissues. Methods and sites may vary, depending on cell and tissue type. Subcutaneous injections are easy to perform and do not need surgical manipulations. Suspension of cells in Matrigel Basement Membrane (BD Biosciences) promotes their anatomical localization and is a commonly used, efficient, and reproducible approach...
April 2, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29572828/the-prognostic-impact-of-differentiation-at-the-invasive-front-of-biliary-tract-cancer
#16
Satoshi Okubo, Shuichi Mitsunaga, Yuichiro Kato, Motohiro Kojima, Motokazu Sugimoto, Naoto Gotohda, Shinichiro Takahashi, Ryuichi Hayashi, Masaru Konishi
BACKGROUND: The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Difinv ) and tumor budding (Bud) in biliary tract cancer (BTC). METHODS: The resected specimen from the 299 BTC patients were examined. Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were found in 16%, 48%, 17%, and 19%, respectively...
March 24, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29567643/structural-centrosome-aberrations-promote-non-cell-autonomous-invasiveness
#17
Olivier Ganier, Dominik Schnerch, Philipp Oertle, Roderick Yh Lim, Marija Plodinec, Erich A Nigg
Centrosomes are the main microtubule-organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein-like protein (NLP), on epithelial spheres grown in Matrigel matrices. We demonstrate that NLP-induced structural centrosome aberrations trigger the escape ("budding") of living cells from epithelia. Remarkably, all cells disseminating into the matrix were undergoing mitosis...
May 2, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29554943/methotrexate-inhibits-effects-of-platelet-derived-growth-factor-and-interleukin-1%C3%AE-on-rheumatoid-arthritis-fibroblast-like-synoviocytes
#18
Beatrice Bergström, Hans Carlsten, Anna-Karin Hultgård Ekwall
BACKGROUND: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro...
March 20, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29534900/does-prophylactic-radiation-therapy-to-avoid-gynecomastia-in-patients-with-prostate-cancer-increase-the-risk-of-breast-cancer
#19
Bjørg Y Aksnessæther, Arne Solberg, Olbjørn H Klepp, Tor Åge Myklebust, Eva Skovlund, Solveig Roth Hoff, Lars J Vatten, Jo-Åsmund Lund
PURPOSE: Prostate cancer (PC) patients who undergo antiandrogen monotherapy are offered prophylactic radiation therapy (PRT) to the breast buds to avoid gynecomastia. The aim of the present study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis was influenced by PRT. METHODS AND MATERIALS: From the Norwegian Cancer Registry, we collected data from all patients with PC as their first cancer diagnosis from 1997 to 2014...
February 5, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29487008/tumor-budding-and-poorly-differentiated-cluster-in-prognostication-in-stage-ii-colon-cancer
#20
Victor Wai Kwan Lee, Kui Fat Chan
Comparison between tumor budding (TB) and poorly-differentiated clusters (PDC) for prognostication in Stage II colon cancer was not extensively studied in literature. In this retrospective study, we assessed TB (according to the consensus statement in 2016) and PDC in 135 Stage II colon adenocarcinoma resection specimens. Counting of TB and PDC was performed on H&E slides. High-grade TB (Bd3 (≥10 tumor buds in 0.785 mm2 )) and high-grade PDC (Grade 3 (≥10)) were found in 20% and 17% of cases respectively...
March 2018: Pathology, Research and Practice
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