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https://www.readbyqxmd.com/read/28823057/fusobacterium-nucleatum-as-a-prognostic-marker-of-colorectal-cancer-in-a-japanese-population
#1
Yuko Yamaoka, Yutaka Suehiro, Shinichi Hashimoto, Tomomi Hoshida, Michiyo Fujimoto, Michiya Watanabe, Daiki Imanaga, Kouhei Sakai, Toshihiko Matsumoto, Mitsuaki Nishioka, Taro Takami, Nobuaki Suzuki, Shoichi Hazama, Hiroaki Nagano, Isao Sakaida, Takahiro Yamasaki
BACKGROUND: Accumulating evidence shows an overabundance of Fusobacterium nucleatum in colorectal tumor tissues. However, the correlation between the absolute copy number of F. nucleatum in colorectal cancer tissues and colorectal cancer progression is unclear from previous reports. Therefore, we performed a study to compare the abundance of F. nucleatum in colorectal tissues with clinicopathologic and molecular features of colorectal cancer. METHODS: We collected 100 colorectal cancer tissues and 72 matched normal-appearing mucosal tissues...
August 19, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28821955/targeted-next-generation-sequencing-for-analyzing-the-genetic-alterations-in-atypical-adenomatous-hyperplasia-and-adenocarcinoma-in-situ
#2
Xuan Xu, Na Li, Ruiying Zhao, Lei Zhu, Jinchen Shao, Jie Zhang
PURPOSE: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level. METHODS: We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel...
August 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28821559/synergy-of-wee1-and-mtor-inhibition-in-mutant-kras-driven-lung-cancers
#3
Josephine Hai, Shengwu Liu, Lauren Bufe, Khanh Do, Ting Chen, Xiaoen Wang, Christine Ng, Shuai Li, Ming-Sound Tsao, Geoffrey I Shapiro, Kwok-Kin Wong
Purpose:KRAS-activating mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multi-targeted therapy may offer a plausible strategy to effectively treat KRAS-driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential therapy for lung cancers harboring KRAS mutations. <p>Experimental Design: We investigated the synergistic effect of combining mTOR and WEE1 inhibitors on cell viability, apoptosis, and DNA damage repair response using a panel of human KRAS-mutant and wild type NSCLC cell lines and patient-derived xenograft cell lines...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28820917/whole-exome-sequencing-of-lacrimal-gland-adenoid-cystic-carcinoma
#4
David W Sant, Wensi Tao, Matthew G Field, Daniel Pelaez, Ke Jin, Anthony Capobianco, Sander R Dubovy, David T Tse, Gaofeng Wang
Purpose: To identify genomic mutations in lacrimal gland adenoid cystic carcinoma (LGACC) samples from patients. Methods: Genomic DNA was extracted from LGACC specimens. Whole exome sequencing (exome-seq) was conducted to screen for mutations. Capillary sequencing was performed to verify mutations in genes shared by multiple samples. Luciferase assays were used to evaluate functional consequences of NOTCH1 mutations. Results: The mutation profile of LGACC was complicated...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28818432/single-color-digital-pcr-provides-high-performance-detection-of-cancer-mutations-from-circulating-dna
#5
Christina Wood-Bouwens, Billy T Lau, Christine M Handy, HoJoon Lee, Hanlee P Ji
We describe a single-color digital PCR assay that detects and quantifies cancer mutations directly from circulating DNA collected from the plasma of cancer patients. This approach relies on a double-stranded DNA intercalator dye and paired allele-specific DNA primer sets to determine an absolute count of both the mutation and wild-type-bearing DNA molecules present in the sample. The cell-free DNA assay uses an input of 1 ng of nonamplified DNA, approximately 300 genome equivalents, and has a molecular limit of detection of three mutation DNA genome-equivalent molecules per assay reaction...
August 11, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28816792/development-of-secondary-acute-myeloid-leukemia-in-a-pediatric-patient-concurrently-receiving-primary-therapy-for-ewing-sarcoma
#6
Brandon R McNew, Benjamin W Darbro, Deqin Ma, David J Gordon
Ewing sarcoma is a pediatric bone and soft tissue sarcoma that requires intensive therapy, which can cause secondary malignancies. We present a rare case of early, treatment-related AML in a pediatric patient concurrently receiving primary therapy for Ewing sarcoma. Despite AML-directed therapy, our patient died secondary to complications of hyperleukocytosis. Cytogenetic and mutation profiling of the leukemia cells revealed the DNA-topoisomerase-II-inhibitor-associated t(9;11)(p22;q23) translocation and clonal KRAS and BRAF mutations...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#7
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28812131/dna-degrades-during-storage-in-formalin-fixed-and-paraffin-embedded-tissue-blocks
#8
Alice Guyard, Alice Boyez, Anaïs Pujals, Cyrielle Robe, Jeanne Tran Van Nhieu, Yves Allory, Julien Moroch, Odette Georges, Jean-Christophe Fournet, Elie-Serge Zafrani, Karen Leroy
Formalin-fixed paraffin-embedded (FFPE) tissue blocks are widely used to identify clinically actionable molecular alterations or perform retrospective molecular studies. Our goal was to quantify degradation of DNA occurring during mid to long-term storage of samples in usual conditions. We selected 46 FFPE samples of surgically resected carcinomas of lung, colon, and urothelial tract, of which DNA had been previously extracted. We performed a second DNA extraction on the same blocks under identical conditions after a median period of storage of 5...
August 15, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28811946/are-all-mutations-the-same-a-rare-case-report-of-coexisting-mutually-exclusive-kras-and-braf-mutations-in-a-patient-with-metastatic-colon-adenocarcinoma
#9
Anusha Vittal, Akshay Middinti, Anup Kasi Loknath Kumar
29-year-old Hispanic woman presented to the clinic with complaints of abdominal pain, nausea, fatigue, and constipation. Laboratory tests indicated the presence of iron deficiency anemia and transaminitis. Imaging evaluation revealed marked hepatomegaly with multiple hepatic metastases and pelvic lymphadenopathy. Biopsy of the hepatic lesions showed adenocarcinoma positive for pan-cytokeratin, CMA5.2, villin, and CDX2. She was positive for tumor markers CA 19-9, CA-125, and CEA. Upon further evaluation, she was found to have colorectal cancer positive for KRAS and BRAF mutations...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28811082/correlation-between-molecular-analysis-diagnosis-according-to-the-2015-who-classification-of-unresected-lung-tumours-and-ttf1-expression-in-small-biopsies-and-cytology-specimens-from-344-non-small-cell-lung-carcinoma-patients
#10
Prudence A Russell, Toni-Maree Rogers, Benjamin Solomon, Naveed Alam, Stephen A Barnett, Vivek Rathi, Richard A Williams, Gavin M Wright, Matthew Conron
We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected...
August 12, 2017: Pathology
https://www.readbyqxmd.com/read/28810144/integrated-genomic-characterization-of-pancreatic-ductal-adenocarcinoma
#11
(no author information available yet)
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28807936/genomic-alterations-in-circulating-tumor-dna-from-diverse-cancer-patients-identified-by-next-generation-sequencing
#12
Maria Schwaederle, Ranajoy Chattopadhyay, Shumei Kato, Paul T Fanta, Kimberly C Banks, In Sil Choi, David E Piccioni, Sadakatsu Ikeda, AmirAli Talasaz, Richard B Lanman, Lyudmila Bazhenova, Razelle Kurzrock
Non-invasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort <p>of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers.</p> The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%) or lung (20.7%). ctDNA obtained from most patients (N = 423 (63%)) displayed at least 1 alteration...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28807782/modulating-protein-protein-interactions-of-the-mitotic-polo-like-kinases-to-target-mutant-kras
#13
Ana J Narvaez, Suzan Ber, Alex Crooks, Amy Emery, Bryn Hardwick, Estrella Guarino Almeida, David J Huggins, David Perera, Meredith Roberts-Thomson, Roberta Azzarelli, Fiona E Hood, Ian A Prior, David W Walker, Richard Boyce, Robert G Boyle, Samuel P Barker, Christopher J Torrance, Grahame J McKenzie, Ashok R Venkitaraman
Mutations activating KRAS underlie many forms of cancer, but are refractory to therapeutic targeting. Here, we develop Poloppin, an inhibitor of protein-protein interactions via the Polo-box domain (PBD) of the mitotic Polo-like kinases (PLKs), in monotherapeutic and combination strategies to target mutant KRAS. Poloppin engages its targets in biochemical and cellular assays, triggering mitotic arrest with defective chromosome congression. Poloppin kills cells expressing mutant KRAS, selectively enhancing death in mitosis...
July 27, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28807210/personalized-treatment-in-patients-with-colorectal-liver-metastases
#14
Dimitrios Moris, Timothy M Pawlik
BACKGROUND: Precision Medicine Initiative is a new research effort aiming to offer personalized treatment in many diseases, including cancer. The aim of the present article is to offer novel insights about the role of personalized treatment in patients with colorectal liver metastases (CRLM). METHODS: A review of the literature regarding personalized medicine and colorectal liver metastases was performed mainly in the MEDLINE/PubMed database. RESULTS: Surgical resection remains the only hope for cure of CRLM...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28807001/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#15
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#16
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28805806/lung-tumor-exome-files-with-t-cell-receptor-recombinations-a-mouse-model-of-t-cell-infiltrates-reflecting-mutation-burdens
#17
Yaping N Tu, Wei Lue Tong, Timothy J Fawcett, George Blanck
Tumor exomes and RNASeq data were originally intended for obtaining tumor mutations and gene expression profiles, respectively. However, recent work has determined that tumor exome and RNAseq read files contain reads representing T-cell and B-cell receptor (TcR and BcR) recombinations, presumably due to infiltrating lymphocytes. Furthermore, the recovery of immune receptor recombination reads has demonstrated correlations with specific, previously appreciated aspects of tumor immunology. To further understand the usefulness of recovering TcR and BcR recombinations from tumor exome files, we developed a scripted algorithm for recovery of reads representing these recombinations from a previously described mouse model of lung tumorigenesis...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28801584/differences-of-protein-expression-profiles-kras-and-braf-mutation-and-prognosis-in-right-sided-colon-left-sided-colon-and-rectal-cancer
#18
Xian Hua Gao, Guan Yu Yu, Hai Feng Gong, Lian Jie Liu, Yi Xu, Li Qiang Hao, Peng Liu, Zhi Hong Liu, Chen Guang Bai, Wei Zhang
To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, β-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801547/early-changes-in-plasma-dna-levels-of-mutant-kras-as-a-sensitive-marker-of-response-to-chemotherapy-in-pancreatic-cancer
#19
Marzia Del Re, Caterina Vivaldi, Eleonora Rofi, Enrico Vasile, Mario Miccoli, Chiara Caparello, Paolo Davide d'Arienzo, Lorenzo Fornaro, Alfredo Falcone, Romano Danesi
Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tumor DNA (cftDNA) could represent a biomarker to monitor chemotherapy response. Twenty-seven advanced PDAC patients given first-line 5-fluorouracil, irinotecan and oxaliplatin or gemcitabine and nab-paclitaxel were enrolled...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801348/incidental-detection-of-germline-variants-of-potential-clinical-significance-by-massively-parallel-sequencing-in-haematological-malignancies
#20
Costas K Yannakou, Kate Jones, Georgina L Ryland, Ella R Thompson, Gareth Reid, Michelle McBean, Alison Trainer, David Westerman, Piers Blombery
Massively parallel sequencing (MPS) technology has become routinely available for diagnosis, prognostication and therapeutic decision-making in haematological malignancies. However, increased throughput and wider coverage of genes can have unintended consequences. Germline variants of potential clinical significance (GVPCSs) detected during cancer testing may have implications for patients and families beyond the biological evaluation of a specific tumour. 721 reports generated from MPS panels used in the routine testing of myeloid and lymphoid malignancies were reviewed and variants within genes of potential germline relevance (TP53, RUNX1, GATA2 and WT1 in all contexts and CBL, KRAS and NRAS in the setting of juvenile myelomonocytic leukaemia) were analysed...
August 11, 2017: Journal of Clinical Pathology
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