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colorectal physiology

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https://www.readbyqxmd.com/read/28636998/physiologically-based-pharmacokinetic-modeling-for-predicting-irinotecan-exposure-in-human-body
#1
Yingfang Fan, Najia Mansoor, Tasneem Ahmad, Rafeeq Alam Khan, Martin Czejka, Syed Sharib, Dong-Hua Yang, Mansoor Ahmed
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623901/biomarker-correlation-network-in-colorectal-carcinoma-by-tumor-anatomic-location
#2
Reiko Nishihara, Kimberly Glass, Kosuke Mima, Tsuyoshi Hamada, Jonathan A Nowak, Zhi Rong Qian, Peter Kraft, Edward L Giovannucci, Charles S Fuchs, Andrew T Chan, John Quackenbush, Shuji Ogino, Jukka-Pekka Onnela
BACKGROUND: Colorectal carcinoma evolves through a multitude of molecular events including somatic mutations, epigenetic alterations, and aberrant protein expression, influenced by host immune reactions. One way to interrogate the complex carcinogenic process and interactions between aberrant events is to model a biomarker correlation network. Such a network analysis integrates multidimensional tumor biomarker data to identify key molecular events and pathways that are central to an underlying biological process...
June 17, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28599275/dicer-suppresses-cytoskeleton-remodeling-and-tumorigenesis-of-colorectal-epithelium-by-mir-324-5p-mediated-suppression-of-hmgxb3-and-wasf-2
#3
Li Na Sun, Cheng Xing, Zheng Zhi, Yao Liu, Liang-Yan Chen, Tong Shen, Qun Zhou, Yu Hong Liu, Wen Juan Gan, Jing-Ru Wang, Yong Xu, Jian Ming Li
Emerging evidence indicates that microRNAs, a class of small and well-conserved noncoding RNAs, participate in many physiological and pathological processes. RNase III endonuclease DICER is one of the key enzymes for microRNA biogenesis. Here, we found that DICER was downregulated in tumor samples of colorectal cancer (CRC) patients at both mRNA and protein levels. Importantly, intestinal epithelial cell (IEC)-specific deletion of Dicer mice got more tumors after azoxymethane and dextran sulfate sodium (DSS) administration...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28593575/the-role-of-herg1-ion-channels-in-epithelial-mesenchymal-transition-and-the-capacity-of-riluzole-to-reduce-cisplatin-resistance-in-colorectal-cancer-cells
#4
Angelo Fortunato
PURPOSE: The transition of cells from the epithelial to the mesenchymal state (EMT) plays an important role in tumor progression. EMT allows cells to acquire mobility, stem-like behavior and resistance to apoptosis and drug treatment. These features turn EMT into a central process in tumor biology. Ion channels are attractive targets for the treatment of cancer since they play critical roles in controlling a wide range of physiological processes that are frequently deregulated in cancer...
June 7, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28588875/management-of-chronic-constipation-in-adults
#5
REVIEW
K Krogh, G Chiarioni, W Whitehead
Chronic constipation (CC) is an extremely common condition with an estimated prevalence of up to 24%. Most patients with CC should be treated in primary care. Changes in lifestyle, including increased intake of dietary fibre, fluid, and exercise, should be attempted in most patients. Osmotic or stimulant laxatives are indicated if there are insufficient effects of lifestyle changes. Prokinetics and secretagogues should be restricted to those not responding to basic treatment. Anorectal physiology tests and assessment of colorectal transit time are indicated if medical treatment fails or if symptoms indicate severely obstructed defecation...
June 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28579842/short-and-long-term-health-consequences-of-sleep-disruption
#6
REVIEW
Goran Medic, Micheline Wille, Michiel Eh Hemels
Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28560691/role-of-tgf-%C3%AE-in-metastatic-colon-cancer-it-is-finally-time-for-targeted-therapy
#7
REVIEW
Maria Villalba, Stephanie R Evans, Fernando Vidal-Vanaclocha, Alfonso Calvo
Colorectal cancer (CRC) is one of the most frequent tumor types in Western countries. Approximately 20 % of patients show metastasis at the time of diagnosis, with the liver being one of the most affected organs. Transforming growth factor-beta (TGF-β) plays a regulatory role not only in the physiology of the normal colon but also in the development of CRC and its metastatic process. In this review, we analyze the molecular mechanisms leading to TGF-β dysregulation in tumor and stroma cells and the modification of the microenvironment that fosters CRC metastasis...
May 30, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28546638/effects-of-obesity-on-liver-cytochromes-p450-in-various-animal-models
#8
Veronika Tomankova, Pavel Anzenbacher, Eva Anzenbacherova
The prevalence of obesity and other obesity-related diseases is increasing worldwide. Obesity is a disease characterized by increased body weight, or a condition resulting from excessive accumulation of body fat. Due to increased body fat deposits, obesity has also been associated with increased mortality resulting from higher incidence rates of hypertension, diabetes, or various types of cancer, such as breast, colorectal, cervical and prostate cancer. Physiological changes associated with obesity are likely to result in altered drug biotransformation...
May 25, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28538040/interleukin-10-592c-a-but-not-1082a-g-promoter-single-nucleotide-polymorphism-is-associated-with-a-decreased-risk-of-colorectal-cancer-in-an-ethnic-kashmiri-population-a-case-control-study
#9
Mujeeb Z Banday, Aga S Sameer, Nissar A Chowdri, Ehtishamul Haq
Chronic inflammation influences the development of various cancers including colorectal cancer (CRC). Interleukin-10 (IL-10), an anti-inflammatory cytokine, plays a vital role in several homeostatic physiological processes occurring in the human gastrointestinal tract including intestinal inflammation and is a key regulator of several gastrointestinal tract pathophysiological processes such as inflammatory bowel diseases that are associated with an increased predisposition to CRC. Several studies have reported the association of various polymorphisms in the human IL-10 gene including IL-10 -592C/A and IL-10 -1082A/G single nucleotide polymorphisms (SNPs) with various cancers including CRC, but these SNPs are yet to be studied in a Kashmiri population with respect to CRC risk...
May 19, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28533661/macrophage-inflammatory-protein-2-as-mediator-of-inflammation-in-acute-liver-injury
#10
REVIEW
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen
Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28498396/diverse-expression-patterns-and-tumorigenic-role-of-neurotensin-signaling-components-in-colorectal-cancer-cells
#11
Ji Tae Kim, Heidi L Weiss, B Mark Evers
Colorectal cancer (CRC), which is one of the most common malignancies worldwide, results from an accumulation of genetic and epigenetic modifications including DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central nervous system, mediates its physiological and pathological effects, including growth stimulation for a variety of cancers, through three distinct NTS receptors (NTSRs). Most NTS functions are mediated through the high-affinity receptor NTSR1, and expression of NTSR1 is increased in many cancers including CRC...
May 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28465216/ros1-protein-tyrosine-kinase-inhibitors-in-the-treatment-of-ros1-fusion-protein-driven-non-small-cell-lung-cancers
#12
REVIEW
Robert Roskoski
ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown...
April 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28455963/trkc-promotes-colorectal-cancer-growth-and-metastasis
#13
Min Soo Kim, Kwang Wook Suh, Suntaek Hong, Wook Jin
The current work reveals that TrkC receptor is crucial to many aspects of tumorigenicity and metastasis of cancer. However, with only a few exceptions, such as colorectal cancer (CRC), where suppressing tumorigenic and metastatic ability via expression of TrkC as tumor suppressor have been proposed. These diverse lines of evidence led us to investigate whether TrkC is involved in CRC progression. By using mouse models and molecular biology analyses, we demonstrate that TrkC acts as an activator in tumorigenicity and metastasis of colorectal cancer...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28451245/protecting-micrornas-from-rnase-degradation-with-steric-dna-nanostructures
#14
H Qian, C Y Tay, M I Setyawati, S L Chia, D S Lee, D T Leong
Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a "shuriken" shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells...
February 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28446191/longitudinal-analysis-of-serum-oxylipin-profile-as-a-novel-descriptor-of-the-inflammatory-response-to-surgery
#15
Arnaud M Wolfer, Alasdair J Scott, Claudia Rueb, Mathieu Gaudin, Ara Darzi, Jeremy K Nicholson, Elaine Holmes, James M Kinross
BACKGROUND: Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the potential to provide novel insights into the physiological response to surgery and the pathophysiology of post-operative complications. We aimed to investigate the effects of major surgery on longitudinal oxylipin profile. METHODS: Adults patients undergoing elective laparoscopic or open colorectal resections were included...
April 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28442534/oncogenic-%C3%AE-catenin-and-pik3ca-instruct-network-states-and-cancer-phenotypes-in-intestinal-organoids
#16
Pamela Riemer, Mattias Rydenfelt, Matthias Marks, Karen van Eunen, Kathrin Thedieck, Bernhard G Herrmann, Nils Blüthgen, Christine Sers, Markus Morkel
Colorectal cancer is driven by cooperating oncogenic mutations. In this study, we use organotypic cultures derived from transgenic mice inducibly expressing oncogenic β-catenin and/or PIK3CA(H1047R) to follow sequential changes in cancer-related signaling networks, intestinal cell metabolism, and physiology in a three-dimensional environment mimicking tissue architecture. Activation of β-catenin alone results in the formation of highly clonogenic cells that are nonmotile and prone to undergo apoptosis. In contrast, coexpression of stabilized β-catenin and PIK3CA(H1047R) gives rise to intestinal cells that are apoptosis-resistant, proliferative, stem cell-like, and motile...
June 5, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28419527/the-rectosigmoid-brake-review-of-an-emerging-neuromodulation-target-for-colorectal-functional-disorders
#17
Anthony Y Lin, Phil G Dinning, Tony Milne, Ian P Bissett, Gregory O'Grady
The regulation of gastrointestinal motility encompasses several overlapping mechanisms including highly regulated and coordinated neurohormonal circuits. Various feedback mechanisms or 'brakes' have been proposed. While duodenal, jejunal, and ileal brakes are well described, a putative distal colonic brake is less well defined. Despite the high prevalence of colonic motility disorders, there is little knowledge of colonic motility owing to difficulties with organ access and technical difficulties in recording detailed motor patterns along its entire length...
April 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28400119/bile-acids-and-colon-cancer-is-fxr-the-solution-of-the-conundrum
#18
REVIEW
Raffaella Maria Gadaleta, Oihane Garcia-Irigoyen, Antonio Moschetta
Diet and lifestyle habits have a profound impact on the pathophysiology of many diseases. Colorectal cancer (CRC) is the third most common cancer worldwide and its etiology is strongly influenced by nutrition and high fat/high carbohydrate Western-style diet. Human epidemiological and animal studies have shown that colonic cancer risk is also related to faecal bile acid concentration. Abnormally high levels of bile acids (BA) trigger the colonic mucosa with a plethora of detrimental effects such as DNA oxidative damage, inflammation and hyperproliferation that highly promote CRC progression in post-initiation phase...
April 8, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28358223/ameliorative-effects-of-pyrazinoic-acid-against-oxidative-and-metabolic-stress-manifested-in-rats-with-dimethylhydrazine-induced-colonic-carcinoma
#19
Anil K Sahdev, Vinit Raj, Ashok K Singh, Amit Rai, Amit K Keshari, Arnab De, Amalesh Samanta, Umesh Kumar, Atul Rawat, Dinesh Kumar, Sneha Nath, Anand Prakash, Sudipta Saha
Pyrazinoic acid (PA) is structurally similar to nicotinic acid which acts on G-protein-coupled receptor (GPR109A). GPR109A expresses in colonic and intestinal epithelial sites, and involves in DNA methylation and cellular apoptosis. Therefore, it may be assumed that PA has similar action like nicotinic acid and may be effective against colorectal carcinoma (CRC). CRC was produced via subcutaneous injection of dimethylhydrazine (DMH) at 40 mg/kg body weight once in a week for 4 weeks. After that, PA was administered orally at 2 doses of 10 and 25 mg/kg daily for 15 d to observe the antiproliferative effect...
March 30, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28350096/cirh1a-augments-the-proliferation-of-rko-colorectal-cancer-cells
#20
Feng Guo, Jian-Jun Chen, Wei-Jun Tang
Accumulating evidence suggests that ribosomal proteins may have extraribosomal functions in various physiological and pathological processes, including cancer. We analyzed the expression of the CIRH1A ribosomal protein in colorectal carcinoma and para-carcinoma samples by bioinformatics analyses of data extracted from The Cancer Genome Atlas and in colorectal cancer cell lines in vitro by qPCR. CIRH1A was highly expressed in carcinoma samples and colorectal cancer cells. We also transduced the RKO colorectal cancer (CRC) cell line with lentivirus-mediated small interfering RNAs (siRNAs) and studied the impact that this knockdown of CIRH1A expression had on cell growth...
April 2017: Oncology Reports
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