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https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#1
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27920630/bilateral-diffuse-pseudoangiomatous-stromal-hyperplasia-pash-causing-gigantomastia-in-a-33-year-old-pregnant-woman-case-report
#2
Natalia Krawczyk, Tanja Fehm, Eugen Ruckhäberle, Svjetlana Mohrmann, Jasmin Riemer, Stefan Braunstein, Jürgen Hoffmann
Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of mammary stroma mostly described as an incidental microscopic finding. Clinically, it can manifest as a palpable, well-circumscribed breast mass or in rare cases as a diffuse bilateral process causing massive breast enlargement. The most postulated theory for aetiology of this condition is hormonal stimulation of mammary myofibroblasts, particularly by progesterone. A definite diagnosis of PASH is based on typical pathological findings like stromal hyperplasia and empty slit-like channels positive for myofibroblastic and negative for endothelial markers...
October 2016: Breast Care
https://www.readbyqxmd.com/read/27919339/the-role-of-gene-mutations-and-gene-products-in-intestinal-tissue-reactions-from-ionising-radiation
#3
Jolyon H Hendry, Kensuke Otsuka
The response of the intestine to (low linear-energy-transfer) ionising radiation is reviewed regarding the cellular basis to the reactions, the regenerative processes which restore the tissue, and external agents which aid its recovery. In the steady-state, it is generally considered that the crypt cell lineages in both small and large intestine are maintained by a small number of stem cells, but there are differences for example in the composition of their niche residence and in the numbers of transit cell generations...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27917295/circulating-human-papillomavirus-dna-detected-using-droplet-digital-pcr-in-the-serum-of-patients-diagnosed-with-early-stage-human-papillomavirus-associated-invasive-carcinoma
#4
Emmanuelle Jeannot, Véronique Becette, Maura Campitelli, Marie-Ange Calméjane, Emmanuelle Lappartient, Evelyne Ruff, Stéphanie Saada, Allyson Holmes, Dominique Bellet, Xavier Sastre-Garau
Specific human papillomavirus genotypes are associated with most ano-genital carcinomas and a large subset of oro-pharyngeal carcinomas. Human papillomavirus DNA is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. However, data concerning circulating human papillomavirus DNA in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. Here we took advantage of the sensitive droplet digital PCR method to identify circulating human papillomavirus DNA in patients with human papillomavirus-associated carcinomas...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27915333/prss8-is-downregulated-and-suppresses-tumour-growth-and-metastases-in-hepatocellular-carcinoma
#5
Li Zhang, Guozhan Jia, Binya Shi, Guanqun Ge, Hongbin Duan, Yunsheng Yang
BACKGROUND: Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC). METHODS: PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed...
December 5, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27913894/use-and-effectiveness-of-tocilizumab-among-patients-with-rheumatoid-arthritis-an-observational-study-from-the-british-society-for-rheumatology-biologics-register-for-rheumatoid-arthritis
#6
Mari Kihara, Rebecca Davies, Lianne Kearsley-Fleet, Kath D Watson, Mark Lunt, Deborah P M Symmons, Kimme L Hyrich
The aims of the present study are to describe the characteristics of rheumatoid arthritis (RA) patients selected for tocilizumab (TCZ), compare the "real-world" effectiveness of TCZ and tumour necrosis factor inhibitors (TNFi) when used as a first biologic and assess the influence of past biologic exposure/concurrent methotrexate (MTX) therapy on post-TCZ treatment outcomes. The British Society for Rheumatology Biologics Register (BSRBR-RA) is a prospective cohort study following RA patients starting biologics in the UK...
December 2, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#7
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27913729/qsea-modelling-of-genome-wide-dna-methylation-from-sequencing-enrichment-experiments
#8
Matthias Lienhard, Sabrina Grasse, Jana Rolff, Steffen Frese, Uwe Schirmer, Michael Becker, Stefan Börno, Bernd Timmermann, Lukas Chavez, Holger Sültmann, Gunda Leschber, Iduna Fichtner, Michal R Schweiger, Ralf Herwig
Genome-wide enrichment of methylated DNA followed by sequencing (MeDIP-seq) offers a reasonable compromise between experimental costs and genomic coverage. However, the computational analysis of these experiments is complex, and quantification of the enrichment signals in terms of absolute levels of methylation requires specific transformation. In this work, we present QSEA, Quantitative Sequence Enrichment Analysis, a comprehensive workflow for the modelling and subsequent quantification of MeDIP-seq data...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#9
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
November 29, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27913042/objective-analysis-of-cancer-stem-cell-marker-expression-using-immunohistochemistry
#10
T J Miller, M J McCoy, C Hemmings, M K Bulsara, B Iacopetta, C F Platell
Analysis of immunohistochemical expression is often a subjective and semiquantitative process that can lead to the inconsistent reporting of results. To assess the effect that region selection and quantification method have on results, five different cancer stem cell markers were used in this study to compare tissue scoring with digital analysis methods that used three different tissue annotation methods. Samples of tumour and normal mucosa were used from 10 consecutive stage II colon cancer patients and stained for the putative cancer stem cell markers ALDH1, CD44v6, CD133, Lgr5 and SOX2...
November 29, 2016: Pathology
https://www.readbyqxmd.com/read/27910812/inflammatory-markers-associated-with-abdominal-aortic-aneurysm
#11
Sarah Lindberg, Moncef Zarrouk, Jan Holst, Anders Gottsäter
PURPOSE: Inflammation with leukocytic infiltration, degradation of extracellular matrix (ECM), and depletion of vascular smooth muscle cells (VSMC) are pathological hallmarks of abdominal aortic aneurysm (AAA). The aim of this study was to further evaluate relationships between AAA and inflammatory biomarkers, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), endothelin-1 (ET-1) and soluble urokinase-type plasminogen activator receptor (suPAR), by comparing levels in 65-year-old men with and without AAA at ultrasound screening...
September 1, 2016: European Cytokine Network
https://www.readbyqxmd.com/read/27909617/diagnostic-value-of-micrornas-in-prostate-cancer-patients-with-prostate-specific-antigen-psa-levels-between-2-and-10-ng-ml
#12
Serin Akbayır, Necati Muşlu, Sema Erden, Murat Bozlu
OBJECTIVE: Prostate specific antigen (PSA), used for the early diagnosis of prostate cancer (PCa), is one of the best tumour markers known so far. However, in situations when PSA is between 2-10 ng/mL, which is named as grey zone, PSA falls short of distinguishing benign prostate diseases from PCa. On the other hand, it was demonstrated in many previous studies that microRNA (miRNA) could be a marker for cancer. Therefore, in this study, it was aimed to enhance the diagnostic power of PSA, especially with grey zone patients, by the use of miRNA...
December 2016: Turkish Journal of Urology
https://www.readbyqxmd.com/read/27907211/characterization-and-immunomodulatory-effects-of-canine-adipose-tissue-and-bone-marrow-derived-mesenchymal-stromal-cells
#13
Keith A Russell, Natalie H C Chow, David Dukoff, Thomas W G Gibson, Jonathan LaMarre, Dean H Betts, Thomas G Koch
BACKGROUND: Mesenchymal stromal cells (MSC) hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies...
2016: PloS One
https://www.readbyqxmd.com/read/27905446/genomic-evolution-and-chemoresistance-in-germ-cell-tumours
#14
Amaro Taylor-Weiner, Travis Zack, Elizabeth O'Donnell, Jennifer L Guerriero, Brandon Bernard, Anita Reddy, G Celine Han, Saud AlDubayan, Ali Amin-Mansour, Steven E Schumacher, Kevin Litchfield, Clare Turnbull, Stacey Gabriel, Rameen Beroukhim, Gad Getz, Scott L Carter, Michelle S Hirsch, Anthony Letai, Christopher Sweeney, Eliezer M Van Allen
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27901069/molecular-profiling-of-circulating-tumour-cells-identifies-notch1-as-a-principal-regulator-in-advanced-non-small-cell-lung-cancer
#15
Javier Mariscal, Marta Alonso-Nocelo, Laura Muinelo-Romay, Jorge Barbazan, Maria Vieito, Alicia Abalo, Antonio Gomez-Tato, Casares de Cal Maria de Los Angeles, Tomas Garcia-Caballero, Carmela Rodriguez, Elena Brozos, Francisco Baron, Rafael Lopez-Lopez, Miguel Abal
Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900589/intrinsic-her2-v777l-mutation-mediates-resistance-to-trastuzumab-in-a-breast-cancer-patient
#16
Yosuke Hirotsu, Hiroshi Nakagomi, Kenji Amemiya, Toshio Oyama, Masayuki Inoue, Hitoshi Mochizuki, Masao Omata
HER2 (ERBB2) is an oncogene and 20% of breast cancers display HER2 amplification. The HER2 monoclonal antibody, trastuzumab, is used to treat breast cancers that display HER2 amplification, with good responses in 80-90% of cases; however, 10% of tumours develop resistance to trastuzumab. In this study, we collected data of primary breast cancer patients who treated at hospital during 2004-2014. In our cohort, 205 of 1497 primary breast cancer patients showed HER2-amplification, and 20 experienced recurrence after trastuzumab therapy...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27899997/testin-tes-as-a-candidate-tumour-suppressor-and-prognostic-marker-in-human-astrocytoma
#17
Giedrius Steponaitis, Arunas Kazlauskas, Daina Skiriute, Indre Valiulyte, Kestutis Skauminas, Arimantas Tamasauskas, Paulina Vaitkiene
Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899993/predictive-value-of-microparticle-associated-tissue-factor-activity-for-permeability-glycoprotein-mediated-multidrug-resistance-in-cancer
#18
Antonio Angelini, Sebastiano Miscia, Maria Antonietta Centurione, Roberta Di Pietro, Lucia Centurione
Multidrug resistance (MDR) protein 1, which is also known as permeability glycoprotein (Pgp), and tissue factor (TF) are recurrently overexpressed on the surface of cancer cells, likely in response to stimuli such as chemotherapy. Microparticles (MPs) released from cancer cells into the bloodstream express tumour markers on their surface that may be useful as predictive biomarkers for evaluating disease progression. The present study measured the level of TF/factor VII (FVII)-dependent coagulation of MPs isolated from the plasma of cancer patients with various tumours, who were undergoing chemotherapy...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898692/targeting-cdks-with-roscovitine-increases-sensitivity-to-dna-damaging-drugs-of-human-osteosarcoma-cells
#19
Serena Vella, Elisa Tavanti, Claudia Maria Hattinger, Marilù Fanelli, Rogier Versteeg, Jan Koster, Piero Picci, Massimo Serra
Cyclin-dependent kinase 2 (CDK2) has been reported to be essential for cell proliferation in several human tumours and it has been suggested as an appropriate target to be considered in order to enhance the efficacy of treatment regimens based on the use of DNA damaging drugs. We evaluated the clinical impact of CDK2 overexpression on a series of 21 high-grade osteosarcoma (OS) samples profiled by using cDNA microarrays. We also assessed the in vitro efficacy of the CDKs inhibitor roscovitine in a panel of drug-sensitive and drug-resistant human OS cell lines...
2016: PloS One
https://www.readbyqxmd.com/read/27898661/methyl-cpg-binding-domain-3-inhibits-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-via-tgf-%C3%AE-smad-signalling
#20
Min Xu, Junbo He, Jie Li, Wen Feng, Hailang Zhou, Hong Wei, Meng Zhou, Ying Lu, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong
BACKGROUND: Methyl-CpG-binding domain 3 (MBD3) is an aberrant expression in human malignancies. However, the role of MBD3 in pancreatic cancer progression remains to be clarified. In this study, we investigated the effects of MBD3 on the epithelial-mesenchymal transition (EMT), and the underlying mechanism in pancreatic cancer cells. METHODS: The abilities of migration and invasion were examined by transwell and BD Matrigel invasion assays. EMT and TGF-β/Smad signalling were evaluated...
November 29, 2016: British Journal of Cancer
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