Israa Imam, Klara Hammarström, Tobias Sjöblom, Bengt Glimelius
INTRODUCTION: The Neoadjuvant Rectal (NAR) score is a new surrogate endpoint to be used in clinical trials for early determination of treatment response to different preoperative therapies. The aim is to further validate the NAR-score, primarily developed using chemoradiotherapy (CRT) with a delay to surgery 6-8 weeks, and explore its value using other schedules. MATERIALS AND METHODS: The study included all 9978 patients diagnosed with non-metastasized RC in 2007-2015 that had undergone surgery and was registered in the Swedish Colorectal Cancer Registry...
January 13, 2021: Radiotherapy and Oncology
Peter Vaughan-Shaw
BACKGROUND: Delay to closure of ileostomy following anterior resection for rectal cancer may impair post-operative bowel function and quality of life (QoL). We analysed time to ileostomy closure across the UK and investigated factors delaying closure. METHODS: Retrospective cohort: We assessed time to closure and incidence of non-closure for patients who underwent anterior resection with defunctioning ileostomy during 2015. Multivariate linear/ cox-regression analyses were performed...
January 16, 2021: Colorectal Disease
Melike Kurt, Zeki Yumuk
The colorectal cancer is a serious health problem. The diagnosis of the disease mostly relies on an invasive procedure. A non-invasive diagnostic test such as an immunoassay, may facilitate diagnosis of colorectal cancer. The purpose of the study was to evaluate the use of antibodies against Fusobacterium nucleatum in the diagnosis of colorectal cancer (CRC). Totally 78 patients in three groups were included in the study. F. nucleatum in the tissues was detected using quantitative polymerase chain reaction assay...
January 15, 2021: Scientific Reports
Bryce McCarthy, Amit Cudykier, Ravi Singh, Nicole Levi-Polyachenko, Shay Soker
Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment. To address this problem tumor organoid technology was used to evaluate the ablative potential of CD44-targeted polymer nanoparticles using hyaluronic acid (HA) as the targeting agent and coating it onto hybrid donor acceptor polymer particles (HDAPPs) to form HA-HDAPPs...
January 15, 2021: Scientific Reports
Loren Gaudet
Dominant understandings of genre-as-form have limited our abilities to perceive health awareness: we recognise, and expect, health awareness campaigns from governmental and non-profit agencies. Inversely, we often fail to recognise, or name, health awareness as such when it comes from other sources, such as commercial marketing or advertisements for products. However, rhetorical genre theory centres attention on action brought about by form and, as such, rhetorical genre provides tools for recognising instances of health awareness often escape our notice...
January 15, 2021: Medical Humanities
D Gareth Evans, Fiona Lalloo, Neil Aj Ryan, Naomi Bowers, Kate Green, Emma R Woodward, Tara Clancy, James Bolton, Rhona J McVey, Andrew J Wallace, Katy Newton, James Hill, Raymond McMahon, Emma J Crosbie
BACKGROUND: Testing cancers for mismatch repair deficiency (dMMR) by immunohistochemistry (IHC) is a quick and inexpensive means of triaging individuals for germline Lynch syndrome testing. The aim of this study was to evaluate tumour dMMR and the prevalence of Lynch syndrome in patients referred to the Manchester Centre for Genomic Medicine, which serves a population of 5.6 million. METHODS: Tumour testing used IHC for MMR proteins with targeted BRAF and MLH1 promotor methylation testing followed by germline mutation and somatic testing as appropriate...
January 15, 2021: Journal of Medical Genetics
Gregory S Cooper, Ashley Grimes, James Werner, Shufen Cao, Pingfu Fu, Kurt C Stange
BACKGROUND: Fecal immunochemical testing (FIT) and multi-target stool DNA testing (mt-sDNA) are recommended colorectal cancer screening options but require follow-up with colonoscopy to determine the source of a positive result. We performed a retrospective analysis in an academic health system to determine adherence to colonoscopy in these patients. METHODS: We identified all patients aged 40 years and older with at least 1 primary care visit who had a positive FIT or mt-sDNA between January 2016 and June 2018...
January 2021: Journal of the American Board of Family Medicine: JABFM
Jeanette M Daly, Kim Parang, Barcey T Levy
INTRODUCTION: Electronic health records (EHRs) are often leveraged in medical research to recruit study participants efficiently. The purpose of this study was to validate and refine the logic of an EHR algorithm for identifying potentially eligible participants for a comparative effectiveness study of fecal immunochemical tests (FITs), using colonoscopy as the standard. METHODS: An Epic report was built to identify patients who met the eligibility criteria to recruit patients having a screening or surveillance colonoscopy...
January 2021: Journal of the American Board of Family Medicine: JABFM
Alejandra Méndez Romero, Wilco Schillemans, Rob van Os, Friederike Koppe, Cornelis J Haasbeek, Ellen M Hendriksen, Karin Muller, Heleen M Ceha, Pètra M Braam, Onne Reerink, Martijn P M Intven, Ines Joye, Edwin P M Jansen, Henrike Westerveld, Merel S Koedijk, Ben J M Heijmen, Jeroen Buijsen
PURPOSE: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. METHODS AND MATERIALS: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium)...
December 29, 2020: International Journal of Radiation Oncology, Biology, Physics
Élie Lambert, Jean-Philippe Babeu, Joël Simoneau, Jennifer Raisch, Laurie Lavergne, Dominique Lévesque, Émilie Jolibois, Mariano Avino, Michelle S Scott, François Boudreau, Francois-Michel Boisvert
HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity...
May 2020: Molecular & Cellular Proteomics: MCP
Elez D Vainer, Juliane Kania-Almog, Ghadeer Zatara, Yishai Levin, Gilad W Vainer
Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon-γ induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon-γ protein temporal regulation in CRC...
October 2020: Molecular & Cellular Proteomics: MCP
Shibnath Ghatak, Vincent C Hascall, Roger R Markwald, Suniti Misra
Cancer initiating cells (CICs) drive tumor formation and drug-resistance, but how they develop drug-resistance characteristics is not well understood. In this study, we demonstrate that chemotherapeutic agent FOLFOX, commonly used for drug-resistant/metastatic colorectal cancer (CRC) treatment, induces overexpression of CD44v6, MDR1, and oncogenic transcription/translation factor Y-box-binding protein-1 (YB-1). Our study revealed that CD44v6, a receptor for hyaluronan, increased the YB-1 expression through PGE2/EP1-mTOR pathway...
January 13, 2021: International Journal of Molecular Sciences
Eun Jung Oh, Woo Seog Sim, Won Gook Wi, Jeayoun Kim, Woo Jin Kim, Jin Young Lee
Despite rapid advancements in laparoscopic surgical techniques and perioperative management, postoperative pain remains a significant clinical issue. We examined the analgesic efficacy of nefopam as an adjuvant in patient-controlled analgesia (PCA) for acute postoperative pain in patients undergoing laparoscopic colorectal cancer surgery. We retrospectively analyzed the medical records of 120 patients who did or did not receive 80 mg of nefopam as an adjuvant in fentanyl PCA; they were allocated to the nefopam ( n = 60) or non-nefopam group ( n = 60)...
January 13, 2021: Journal of Clinical Medicine
Muhammad Azizan Samad, Mohd Zuwairi Saiman, Nazia Abdul Majid, Saiful Anuar Karsani, Jamilah Syafawati Yaacob
Colorectal cancer (CRC) is the most common cancer among males and females, which is associated with the increment of telomerase level and activity. Some plant-derived compounds are telomerase inhibitors that have the potential to decrease telomerase activity and/or level in various cancer cell lines. Unfortunately, a deeper understanding of the effects of telomerase inhibitor compound(s) on CRC cells is still lacking. Therefore, in this study, the aspects of telomerase inhibitors on a CRC cell line (HCT 116) were investigated...
January 13, 2021: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Osman Ali, Mazen Tolaymat, Shien Hu, Guofeng Xie, Jean-Pierre Raufman
Despite great advances in our understanding of the pathobiology of colorectal cancer and the genetic and environmental factors that mitigate its onset and progression, a paucity of effective treatments persists. The five-year survival for advanced, stage IV disease remains substantially less than 20%. This review examines a relatively untapped reservoir of potential therapies to target muscarinic receptor expression, activation, and signaling in colorectal cancer. Most colorectal cancers overexpress M3 muscarinic receptors (M3 R), and both in vitro and in vivo studies have shown that activating these receptors stimulates cellular programs that result in colon cancer growth, survival, and spread...
January 13, 2021: International Journal of Molecular Sciences
Wei-Qing Liu, Wen-Liang Li, Shu-Min Ma, Lei Liang, Zhi-Yong Kou, Jun Yang
In this study, we aimed to uncover genes that drive the pathogenesis of liver metastasis in colorectal cancer (CRC), and identify effective genes that could serve as potential therapeutic targets for treating with colorectal liver metastasis patients based on two GEO datasets. Several bioinformatics approaches were implemented. First, differential expression analysis screened out key differentially expressed genes (DEGs) across the two GEO datasets. Based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we identified the enrichment functions and pathways of the DEGs that were associated with liver metastasis in CRC...
January 12, 2021: Translational Oncology
Yi Liu, Meng Yue, Ze Li
Colorectal carcinoma (CC), one of the most prevalent digestive cancers with high mortality and morbidity globally, still lacks powerful therapies to improve the prognosis. Here, we established that the expression of fos-like antigen-1 (Fosl1) was elevated in CC tissues versus adjacent tissues. Importantly, high Fosl1 expression was related to dismal prognosis among CC patients. Functional assays displayed that Fosl1 increased the viability, epithelial-to-mesenchymal transition (EMT), migration and invasion of CC cells...
January 12, 2021: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Chang Li, Yuning Zhou, Ji Tae Kim, Tomoko Sengoku, Michael C Alstott, Heidi L Weiss, Qingding Wang, B Mark Evers
Activation of the Wnt/□-catenin pathway is one of the hallmarks of colorectal cancer (CRC). Sirtuin 2 (SIRT2) protein has been shown to inhibit CRC proliferation. Previously, we reported that SIRT2 plays an important role in the maintenance of normal intestinal cell homeostasis. Here, we show that SIRT2 is a direct target gene of Wnt/□-catenin signaling in CRC cells. Inhibition or knockdown of Wnt/□-catenin increased SIRT2 promoter activity and mRNA and protein expression, whereas activation of Wnt/□-catenin decreased SIRT2 promoter activity and expression...
January 12, 2021: Biochimica et Biophysica Acta. Molecular Cell Research
Ramazan Rezaei, Kaveh Baghaei, Davar Amani, Andrea Piccin, Seyed Mahmoud Hashemi, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali
AIMS: EMT is the process by which a polarized epithelial cell undergoes several changes leading to highly invasive and fibroblast-like morphology. It has been described that miR-375 is inversely associated with EMT in cancerous patients and can effectively inhibit invasion and migration of tumor cells. Here, we investigate whether miR-375 mimic delivered by tumor-derived exosomes could reverse EMT process. MAIN METHODS: The exosomes were isolated from HT-29 and SW480...
January 12, 2021: Life Sciences
Hannes Hagström, Nelson Ndegwa, Molly Jalmeus, Mattias Ekstedt, Iris Posserud, Fredrik Rorsman, Nils Nyhlin, Daniel Klintman, Mårten Werner, Hanns-Ulrich Marschall, Johan Askling, Per Stål
BACKGROUND & AIMS: Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. METHODS: We identified 3,645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population...
January 15, 2021: Liver International: Official Journal of the International Association for the Study of the Liver
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