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https://www.readbyqxmd.com/read/28445943/a-molecular-inversion-probe-based-next-generation-sequencing-panel-to-detect-germline-mutations-in-chinese-early-onset-colorectal-cancer-patients
#1
Junxiao Zhang, Xiaoyan Wang, Richarda M de Voer, Jayne Y Hehir-Kwa, Eveline J Kamping, Robbert D A Weren, Marcel Nelen, Alexander Hoischen, Marjolijn J L Ligtenberg, Nicoline Hoogerbrugge, Xiangling Yang, Zihuan Yang, Xinjuan Fan, Lei Wang, Huanliang Liu, Jianping Wang, Roland P Kuiper, Ad Geurts van Kessel
The currently known Mendelian colorectal cancer (CRC) predisposition syndromes account for ~5-10% of all CRC cases, and are caused by inherited germline mutations in single CRC predisposing genes. Using molecular inversion probes (MIPs), we designed a targeted next-generation sequencing panel to identify mutations in seven CRC predisposing genes: APC, MLH1, MSH2, MSH6, PMS2, MUTYH and NTHL1. From a consecutive series of 2,371 Chinese CRC patients, 140 familial and non-familial cases were selected that were diagnosed with CRC at or below the age of 35 years...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445728/blocking-surgically-induced-lysyl-oxidase-activity-reduces-the-risk-of-lung-metastases
#2
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445136/selective-eradication-of-cancer-cells-by-delivery-of-adenovirus-based-toxins
#3
Shiran Shapira, Assaf Shapira, Diana Kazanov, Gil Hevroni, Sarah Kraus, Nadir Arber
BACKGROUND AND OBJECTIVE: KRAS mutation is an early event in colorectal cancer carcinogenesis. We previously reported that a recombinant adenovirus, carrying a pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was previously tried and failed repeatedly. We aim to improve efficacy by substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin-antitoxin system, under a very tight regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440429/cathepsin%C3%A2-b-expression-in-colorectal-cancer-in-a-middle-east-population-potential-value-as-a-tumor-biomarker-for-late-disease-stages
#4
Maha-Hamadien Abdulla, Mansoor-Ali Valli-Mohammed, Khayal Al-Khayal, Abdulmalik Al Shkieh, Ahmad Zubaidi, Rehan Ahmad, Khalid Al-Saleh, Omar Al-Obeed, James McKerrow
Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA) family. The diagnostic and prognostic significance of increased CTSB in the serum of cancer patients have been evaluated for some tumor types. CTSB serum and protein levels have also been reported previously in colorectal cancer (CRC) with contradictory results. The aim of the present study was to investigate CTSB expression in CRC patients and the association of CTSB expression with various tumor stages in a Middle East population...
April 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439604/emergency-presentation-of-colorectal-cancer-in-northwestern-saudi-arabia
#5
Ibrahim A Albalawi, Ahmad A Abdullah, Mohammed E Mohammed
To investigate the frequency and clinical characteristics of emergency presentation of colorectal carcinoma (CRC) in Tabuk Region of Saudi Arabia.  Methods: This is a retrospective, descriptive hospital-based study. All cases with CRC that presented to the main referral hospitals in Tabuk, Saudi Arabia between 2010 and 2015 were retrieved. The relevant hospitals are: King Salman Military Hospital, King Khalid Hospital, and King Fahad Hospital.  Results: Seventy-three patients were included in the study...
May 2017: Saudi Medical Journal
https://www.readbyqxmd.com/read/28438617/tumor-budding-as-a-risk-factor-for-nodal-metastasis-in-pt1-colorectal-cancers-a-meta-analysis
#6
Rocco Cappellesso, Claudio Luchini, Nicola Veronese, Marcello Lo Mele, Erik Rosa-Rizzotto, Ennio Guido, Franca De Lazzari, Pierluigi Pilati, Fabio Farinati, Stefano Realdon, Marco Solmi, Matteo Fassan, Massimo Rugge
Worldwide, colorectal cancer (CRC) screening programs have significantly increased the detection of sub-mucosal (pT1) adenocarcinoma. Completion surgery may be indicated after endoscopic excision of these potentially metastasizing early cancers. However, the post-surgical prevalence of nodal implants does not exceed 15%, leading to questions concerning the clinical appropriateness of any post-endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer of the Colon-Rectum, in particular) include tumor budding (TB), defined as the presence of isolated single cancer cells or clusters of fewer than five cancer cells at the tumor invasive front, among the variables that must be included in histological reports...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28434582/effectiveness-between-early-and-late-temporary-ileostomy-closure-in-patients-with-rectal-cancer-a-prospective-study
#7
Li Zhen, Yanan Wang, Ze Zhang, Tongwei Wu, Ruoyan Liu, Tingting Li, Liying Zhao, Haijun Deng, Xiaolong Qi, Guoxin Li
A temporary stoma is often used in rectal cancer surgery to protect a distal anastomosis, which remains a major concern after rectal cancer surgery, particularly after low anterior resection. The temporary stoma is scheduled for closure. However, the optimal time of closure of the protecting stoma remains unclear because of sparse studies and data. We aimed to detect the efficacy between early and late temporary ileostomy closure in patients with rectal cancer during or after neoadjuvant chemoradiotherapy. We conducted a prospective, 2-group design between early and late ileostomy closure group in patients after rectal cancer surgery with temporary stoma...
March 2, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28432610/left-versus-right-does-location-matter-for-refractory-metastatic-colorectal-cancer-patients-in-phase-1-clinical-trials
#8
Sukeshi Patel Arora, Norma S Ketchum, Joel Michalek, Jonathon Gelfond, Devalingam Mahalingam
PURPOSE: Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies. METHODS: A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012...
April 22, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28428272/hur-small-molecule-inhibitor-elicits-differential-effects-in-adenomatosis-polyposis-and-colorectal-carcinogenesis
#9
Michaela Lang, David Berry, Katharina Passecker, Ildiko Mesteri, Sabin Bhuju, Florian Ebner, Vitaly Sedlyarov, Rayko Evstatiev, Kyle Dammann, Alexander Loy, Orest Kuzyk, Pavel Kovarik, Vineeta Khare, Martin Beibel, Guglielmo Roma, Nicole Meisner-Kober, Christoph Gasche
HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3' untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427088/a-phase-2-study-of-temozolomide-in-pretreated-metastatic-colorectal-cancer-with-mgmt-promoter-methylation
#10
M A Calegari, A Inno, S Monterisi, A Orlandi, D Santini, M Basso, A Cassano, M Martini, T Cenci, I de Pascalis, F Camarda, B Barbaro, L M Larocca, S Gori, G Tonini, C Barone
BACKGROUND: Presently, few options are available for refractory colorectal cancer (CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a frequent and early event in CRC tumourigenesis. This epigenetic silencing is a predictor of response to the alkylating drug temozolomide in glioblastoma. Preclinical evidences and some case reports showed temozolomide activity in CRC with MGMT silencing, but the available data from clinical trials are inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according to a two-stage Simon's optimal design to investigate activity and safety of temozolomide in refractory CRC harbouring MGMT promoter methylation...
April 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28425574/factors-associated-with-sustainability-of-2-quality-improvement-programs-after-achieving-early-implementation-success-a-qualitative-case-study
#11
Stephanie M C Ament, Freek Gillissen, Albine Moser, José M C Maessen, Carmen D Dirksen, Maarten F von Meyenfeldt, Trudy van der Weijden
RATIONALE, AIMS, AND OBJECTIVES: Sustainability of innovations is a relatively new concept in health care research and has become an issue of growing interest. The current study explored factors related to the sustainability of 2 multidisciplinary hospital-based programs 3 to 6 years after achieving early implementation success. METHOD: An exploratory qualitative study was conducted into 2 implementation cases, an Enhanced Recovery After Surgery program for colorectal surgery and a short-stay program for breast cancer surgery...
April 20, 2017: Journal of Evaluation in Clinical Practice
https://www.readbyqxmd.com/read/28424871/final-analysis-of-the-randomised-peak-trial-overall-survival-and-tumour-responses-during-first-line-treatment-with-mfolfox6-plus-either-panitumumab-or-bevacizumab-in-patients-with-metastatic-colorectal-carcinoma
#12
Fernando Rivera, Meinolf Karthaus, J Randolph Hecht, Isabel Sevilla, Frédéric Forget, Gianpiero Fasola, Jean-Luc Canon, Xuesong Guan, Gaston Demonty, Lee S Schwartzberg
PURPOSE: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective...
April 19, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28424071/imatinib-treatment-of-poor-prognosis-mesenchymal-type-primary-colon-cancer-a-proof-of-concept-study-in-the-preoperative-window-period-impacct
#13
I Ubink, H J Bloemendal, S G Elias, M A Brink, M P Schwartz, Y C W Holierhoek, P M Verheijen, A W Boerman, R H J Mathijssen, W W J de Leng, R A de Weger, W M U van Grevenstein, M Koopman, M P Lolkema, O Kranenburg, I H M Borel Rinkes
BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer...
April 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28424049/findings-in-young-adults-at-colonoscopy-from-a-hospital-service-database-audit
#14
Stephanie Wong, Ilmars Lidums, Christophe Rosty, Andrew Ruszkiewicz, Susan Parry, Aung Ko Win, Yoko Tomita, Sina Vatandoust, Amanda Townsend, Dainik Patel, Jennifer E Hardingham, David Roder, Eric Smith, Paul Drew, Julie Marker, Wendy Uylaki, Peter Hewett, Daniel L Worthley, Erin Symonds, Graeme P Young, Timothy J Price, Joanne P Young
BACKGROUND: Colorectal cancer (CRC) diagnosed at <50 years is predominantly located in the distal colon and rectum. Little is known about which lesion subtypes may serve as CRC precursors in young adults. The aim of this work was to document the prevalence and histological subtype of lesions seen in patients aged <50 years, and any associated clinical features. METHODS: An audit of the colonoscopy database at The Queen Elizabeth Hospital in Adelaide, South Australia over a 12-month period was undertaken...
April 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28423721/downregulation-of-phosphorylated-mkk4-is-associated-with-a-poor-prognosis-in-colorectal-cancer-patients
#15
Wang Pu-Ning, Huang Jun, Duan Ying-Hua, Zhou Jia-Min, Huang Pin-Zhu, Fan Xin-Juan, Huang Yan, Wang Lei, Liu Huan-Liang, Wang Jian-Ping, Huang Mei-Jin
Mitogen-activated protein kinase kinase 4 (MKK4) is a key mediator of Jun N-terminal kinase signaling and influences malignant metastasis. Here, we used immunohistochemistry to assess phosphorylated MMK4 (pMKK4) levels and examine their association with the clinicopathological features of a pilot set of patient samples consisting of normal colonic mucosa (NCM), colorectal adenoma (CA), and colorectal cancer (CRC) tissues. pMKK4 levels were also assessed in a validation set of CRC cases with accompanying follow-up data to confirm their clinicopathological and prognostic significance...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423643/pole-and-pold1-screening-in-155-patients-with-multiple-polyps-and-early-onset-colorectal-cancer
#16
Clara Esteban-Jurado, David Giménez-Zaragoza, Jenifer Muñoz, Sebastià Franch-Expósito, Miriam Álvarez-Barona, Teresa Ocaña, Miriam Cuatrecasas, Sabela Carballal, María López-Cerón, Maria Marti-Solano, Marcos Díaz-Gay, Tom van Wezel, Antoni Castells, Luis Bujanda, Judith Balmaña, Victoria Gonzalo, Gemma Llort, Clara Ruiz-Ponte, Joaquín Cubiella, Francesc Balaguer, Rosa Aligué, Sergi Castellví-Bel
Germline mutations in POLE and POLD1 have been shown to cause predisposition to colorectal multiple polyposis and a wide range of neoplasms, early-onset colorectal cancer being the most prevalent. In order to find additional mutations affecting the proofreading activity of these polymerases, we sequenced its exonuclease domain in 155 patients with multiple polyps or an early-onset colorectal cancer phenotype without alterations in the known hereditary colorectal cancer genes. Interestingly, none of the previously reported mutations in POLE and POLD1 were found...
March 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423572/acceleration-of-leukocytes-epigenetic-age-as-an-early-tumor-and-sex-specific-marker-of-breast-and-colorectal-cancer
#17
Danielle Fernandes Durso, Maria Giulia Bacalini, Claudia Sala, Chiara Pirazzini, Elena Marasco, Massimiliano Bonafé, Ítalo Faria do Valle, Davide Gentilini, Gastone Castellani, Ana Maria Caetano Faria, Claudio Franceschi, Paolo Garagnani, Christine Nardini
Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423551/metabolic-reprogramming-of-the-premalignant-colonic-mucosa-is-an-early-event-in-carcinogenesis
#18
Mart Dela Cruz, Sarah Ledbetter, Sanjib Chowdhury, Ashish K Tiwari, Navneet Momi, Ramesh K Wali, Charles Bliss, Christopher Huang, David Lichtenstein, Swati Bhattacharya, Anisha Varma-Wilson, Vadim Backman, Hemant K Roy
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423493/clinical-significance-of-detecting-circulating-tumor-cells-in-colorectal-cancer-using-subtraction-enrichment-and-immunostaining-fluorescence-in-situ-hybridization-se-ifish
#19
Wei Wu, Zhenzhen Zhang, Xian Hua Gao, Zhen Shen, Yan Jing, Haibo Lu, Heng Li, Xiaoye Yang, Xiangbin Cui, Yuqing Li, Zheng Lou, Peng Liu, Cun Zhang, Wei Zhang
Circulating tumor cells (CTC) are useful in early detection of colorectal cancer. This study described a newly developed platform, integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), to assess CTCs in colorectal cancer. CTCs were detected by SE-iFISH in 40 of 44 preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%, which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033). No significant association was found between tumor stage, survival and preoperative CTC number...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423402/multiple-roles-of-apc-and-its-therapeutic-implications-in-colorectal-cancer
#20
Lu Zhang, Jerry W Shay
Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene highly mutated in colorectal cancers (CRC). Mutation and inactivation of this gene is a key and early event almost uniquely observed in colorectal tumorigenesis. Alterations in the APC gene generate truncated gene products, leading to activation of the Wnt signaling pathway and deregulation of multiple other cellular processes. It has been a mystery why most patients with CRC retain a truncated APC protein, but accumulating evidence suggest that these C terminally truncated APC proteins may have gain of function properties beyond the well-established loss of tumor suppressive function...
August 1, 2017: Journal of the National Cancer Institute
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