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https://www.readbyqxmd.com/read/28718829/aspirin-prevention-of-colorectal-cancer-focus-on-nf-%C3%AE%C2%BAb-signalling-and-the-nucleolus
#1
REVIEW
Jingyu Chen, Lesley A Stark
Overwhelming evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have anti-tumour activity and the potential to prevent cancer, particularly colorectal cancer. However, the mechanisms underlying this effect remain hypothetical. Dysregulation of the nuclear factor-kappaB (NF-κB) transcription factor is a common event in many cancer types which contributes to tumour initiation and progression by driving expression of pro-proliferative/anti-apoptotic genes. In this review, we will focus on the current knowledge regarding NSAID effects on the NF-κB signalling pathway in pre-cancerous and cancerous lesions, and the evidence that these effects contribute to the anti-tumour activity of the agents...
July 18, 2017: Biomedicines
https://www.readbyqxmd.com/read/28717396/intraoperative-radiotherapy-review-of-techniques-and-results
#2
REVIEW
Avinash Pilar, Meetakshi Gupta, Sarbani Ghosh Laskar, Siddhartha Laskar
Intraoperative radiotherapy (IORT) is a technique that involves precise delivery of a large dose of ionising radiation to the tumour or tumour bed during surgery. Direct visualisation of the tumour bed and ability to space out the normal tissues from the tumour bed allows maximisation of the dose to the tumour while minimising the dose to normal tissues. This results in an improved therapeutic ratio with IORT. Although it was introduced in the 1960s, it has seen a resurgence of popularity with the introduction of self-shielding mobile linear accelerators and low-kV IORT devices, which by eliminating the logistical issues of transport of the patient during surgery for radiotherapy or building a shielded operating room, has enabled its wider use in the community...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28714375/the-association-of-mir-126-3p-mir-126-5p-and-mir-664-3p-expression-profiles-with-outcomes-of-patients-with-metastatic-colorectal-cancer-treated-with-bevacizumab
#3
Ondrej Fiala, Pavel Pitule, Petr Hosek, Vaclav Liska, Ondrej Sorejs, Jan Bruha, Ondrej Vycital, Tomas Buchler, Alexandr Poprach, Ondrej Topolcan, Jindrich Finek
MicroRNAs regulate the expression of genes involved in several important cancer-related processes including cell adhesion, proliferation, and tumour angiogenesis. Bevacizumab is routinely used in the treatment of patients with metastatic colorectal cancer, but, so far, no reliable biomarker predicting response to bevacizumab has been established. The aim of our retrospective study was to evaluate the association of miR-126-3p, miR-126-5p and miR-664-3p tumour expression levels with outcomes of patients with metastatic colorectal cancer treated with bevacizumab...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28712119/circulating-activin-a-predicts-survival-in-cancer-patients
#4
Audrey Loumaye, Marie de Barsy, Maxime Nachit, Pascale Lause, Aline van Maanen, Pierre Trefois, Damien Gruson, Jean-Paul Thissen
BACKGROUND: Several experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients. Our goal was therefore to investigate the value of ActA to predict survival in cancer patients. METHODS: Patients with colorectal or lung cancer were prospectively enrolled at the time of diagnosis or relapse between January 2012 and March 2014...
July 15, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28707587/immunotherapeutic-interleukin-6-or-interleukin-6-receptor-blockade-in-cancer-challenges-and-opportunities
#5
Nirmala C Kampan, Sue D Xiang, Orla M McNally, Andrew N Stephens, Michael A Quinn, Magdalena Plebanski
Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic activity is a central player in chronic inflammatory diseases including cancers. Therefore, blockade of the IL-6 signaling pathway has become a target for the therapy of in diverse cancers such as multicentric Castleman's disease (CD), multiple myeloma and solid tumours including renal, prostate, lung, colorectal and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6 receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone or in combination with conventional chemotherapy...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28704212/endoscopic-mucosal-resection-and-endoscopic-submucosal-dissection-technique-and-new-directions
#6
Toshihiro Nishizawa, Naohisa Yahagi
PURPOSE OF REVIEW: Most of small tumours in gastrointestinal tract are easily removed by endoscopic mucosal resection (EMR). However, EMR are sometimes not reliable to ensure the complete resection for large tumours. Although endoscopic submucosal dissection (ESD) was developed, it had a higher risk for complications such as perforation and bleeding. The techniques and clinical outcomes of EMR and ESD are reviewed. RECENT FINDINGS: ESD is more effective for early gastric and oesophageal cancer with higher en-bloc resection rate and lower local recurrence in comparison to EMR...
July 12, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28695389/clinicopathological-determinants-of-an-elevated-systemic-inflammatory-response-following-elective-potentially-curative-resection-for-colorectal-cancer
#7
David G Watt, Michelle L Ramanathan, Stephen T McSorley, Killian Walley, James H Park, Paul G Horgan, Donald C McMillan
INTRODUCTION: The postoperative systemic inflammatory response (SIR) is related to both long- and short-term outcomes following surgery for colorectal cancer. However, it is not clear which clinicopathological factors are associated with the magnitude of the postoperative SIR. The present study was designed to determine the clinicopathological determinants of the postoperative systemic inflammatory response following colorectal cancer resection. METHODS: Patients with a histologically proven diagnosis of colorectal cancer who underwent elective, potentially curative resection during a period from 1999 to 2013 were included in the study (n = 752)...
July 10, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28693799/the-current-value-of-determining-the-mismatch-repair-status-of-colorectal-cancer-a-rationale-for-routine-testing
#8
REVIEW
E Ryan, K Sheahan, B Creavin, H M Mohan, D C Winter
Colorectal Cancer (CRC) is the third most prevalent cancer in men and women. Up to 15% of CRCs display microsatellite instability (MSI). MSI is reflective of a deficient mismatch repair (MMR) system and is most commonly caused by hypermethylation of the MLH1 promoter. However, it may also be due to autosomal dominant constitutional mutations in DNA MMR, termed Lynch Syndrome. MSI may be diagnosed via polymerase chain reaction (PCR) or alternatively, immunohistochemistry (IHC) can identify MMR deficiency (dMMR)...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28692055/cellular-prion-protein-prp-c-in-the-development-of-merlin-deficient-tumours
#9
L Provenzano, Y Ryan, D A Hilton, J Lyons-Rimmer, F Dave, E A Maze, C L Adams, R Rigby-Jones, S Ammoun, C O Hanemann
Loss of function mutations in the neurofibromatosis Type 2 (NF2) gene, coding for a tumour suppressor, Merlin, cause multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas. These tumours may occur sporadically or as part of the hereditary condition neurofibromatosis Type 2 (NF2). Current treatment is confined to (radio) surgery and no targeted drug therapies exist. NF2 mutations and/or Merlin inactivation are also seen in other cancers including some mesothelioma, breast cancer, colorectal carcinoma, melanoma and glioblastoma...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28692044/pyruvate-dehydrogenase-kinase-4-exhibits-a-novel-role-in-the-activation-of-mutant-kras-regulating-cell-growth-in-lung-and-colorectal-tumour-cells
#10
A G Trinidad, N Whalley, R Rowlinson, O Delpuech, P Dudley, C Rooney, S E Critchlow
RAS signalling is involved in the control of several metabolic pathways including glycolysis, mitochondrial respiration and glutamine metabolism. Importantly, we have found here that loss of PDHK4, a key regulator of the pyruvate dehydrogenase complex, caused a profound cell growth inhibition in tumour cells harbouring KRAS mutations. Using isogenic cells and a panel of colorectal and lung cell lines we demonstrated that KRAS mutant cells showed a dependency on PDHK4 whereas KRAS wild-type cells were significantly resistant to PDHK4 knockdown...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28687169/pitfalls-in-diagnosing-colon-cancer-on-abdominal-ct
#11
E Klang, M Eifer, U Kopylov, V Belsky, S Raskin, E Konen, M M Amitai
AIM: To assess the frequency of undetected colon cancer on conventional abdominal CT and to evaluate the imaging features that are characteristic of those cancers. MATERIALS AND METHODS: The present study included consecutive patients diagnosed with colorectal cancer at colonoscopy (2006-2015) who also underwent abdominal computed tomography (CT) performed for various reasons within a year prior to the colonoscopy. The frequency of undetected lesions was evaluated for the original CT interpretations ("original readers")...
July 4, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28683472/comprehensive-analysis-of-copy-number-aberrations-in-microsatellite-stable-colon-cancer-in-view-of-stromal-component
#12
M Henar Alonso, Susanna Aussó, Adriana Lopez-Doriga, David Cordero, Elisabet Guinó, Xavier Solé, Mercè Barenys, Javier de Oca, Gabriel Capella, Ramón Salazar, Rebeca Sanz-Pamplona, Victor Moreno
BACKGROUND: Somatic copy number aberrations (CNAs) are common acquired changes in cancer cells having an important role in the progression of colon cancer (colorectal cancer, CRC). This study aimed to perform a characterisation of CNA and their impact in gene expression. METHODS: Copy number aberrations were inferred from SNP array data in a series of 99 CRC. Copy number aberration events were calculated and used to assess the association between copy number dosage, clinical and molecular characteristics of the tumours, and gene expression changes...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28682829/tumour-growth-increased-following-antiangiogenic-interruption-the-challenge-of-tumour-evaluation
#13
Sarra Oumrani, Marie-Anne Guillaumot, Bertrand Brieau, Ammar Oudjit, Chloé Léandri, Catherine Brezault, Stanislas Chaussade, Romain Coriat
Vascular endothelial growth factor inhibitors, led by bevacizumab, are considered the cornerstone of the therapy in metastatic colorectal carcinoma. We present the case of a patient with metastatic colorectal cancer who experienced rapid tumour growth with liver broad invasion after the withdrawal of an antivascular endothelial growth factor therapy, aflibercept. The rebound effect caused by the residual tumour inducing a regrowth after an initial controlled disease has already been stressed in mice and metastatic colorectal cancer patients following bevacizumab interruption...
July 5, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28678043/current-use-of-mri-in-patients-with-liver-metastatic-colorectal-cancer-a-population-based-study
#14
Laurianne Pech, Jean-Pierre Cercueil, Valérie Jooste, Denis Krause, Olivier Facy, Anne-Marie Bouvier
BACKGROUND: Liver MRI is recommended as the preoperative imaging strategy in liver metastatic colorectal cancers. OBJECTIVE: The aim of the study was to assess for the first time the use of liver MRI in a French population-based cancer registry. PATIENTS AND METHODS: All liver-only metastatic colorectal cancers resected for their primary tumour diagnosed between 2009 and 2013 were included. Nonconditional logistic regression was used to search for associations between the MRI order and the characteristics of patients and tumours...
July 3, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28677162/the-clinical-impact-of-tumour-infiltrating-lymphocytes-in-colorectal-cancer-differs-by-anatomical-subsite-a-cohort-study
#15
Jonna Berntsson, Maria C Svensson, Karin Leandersson, Björn Nodin, Patrick Micke, Anna H Larsson, Jakob Eberhard, Karin Jirström
Accumulating evidence demonstrates an association between dense infiltration of lymphocytes and prognosis in colorectal cancer (CRC), but whether this prognostic impact differs by tumour location remains unknown. This study investigated the prognostic impact of cytotoxic and regulatory T cells in CRC, with particular reference to the anatomical subsite of the primary tumour. The density of CD3(+) , CD8(+) , and FoxP3(+) tumour-infiltrating T cells was calculated in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort...
July 5, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28676564/calcium-intake-and-risk-of-colorectal-cancer-according-to-expression-status-of-calcium-sensing-receptor-casr
#16
Wanshui Yang, Li Liu, Yohei Masugi, Zhi Rong Qian, Reiko Nishihara, NaNa Keum, Kana Wu, Stephanie Smith-Warner, Yanan Ma, Jonathan A Nowak, Fatemeh Momen-Heravi, Libin Zhang, Michaela Bowden, Teppei Morikawa, Annacarolina da Silva, Molin Wang, Andrew T Chan, Charles S Fuchs, Jeffrey A Meyerhardt, Kimmie Ng, Edward Giovannucci, Shuji Ogino, Xuehong Zhang
OBJECTIVE: Although evidence suggests an inverse association between calcium intake and the risk of colorectal cancer, the mechanisms remain unclear. The calcium-sensing receptor (CASR) is expressed abundantly in normal colonic epithelium and may influence carcinogenesis. We hypothesized that calcium intake might be associated with lower risk of CASR-positive, but not CASR-negative, colorectal cancer. DESIGN: We assessed tumour CASR protein expression using immunohistochemistry in 779 incident colon and rectal cancer cases that developed among 136 249 individuals in the Nurses' Health Study and Health Professionals Follow-Up Study...
July 4, 2017: Gut
https://www.readbyqxmd.com/read/28669749/extracellular-vesicles-in-gastrointestinal-cancer-in-conjunction-with-microbiota-on-the-border-of-kingdoms
#17
REVIEW
Natasha S Barteneva, Yeldar Baiken, Elizaveta Fasler-Kan, Kenneth Alibek, Sheng Wang, Natalia Maltsev, Eugeny D Ponomarev, Zarina Sautbayeva, Sholpan Kauanova, Anna Moore, Christoph Beglinger, Ivan A Vorobjev
Extracellular vesicle (EV) production is a universal feature of metazoan cells as well as prokaryotes (bMVs - bacterial microvesicls). They are small vesicles with phospholipid membrane carrying proteins, DNA and different classes of RNAs and are heavily involved in intercellular communication acting as vectors of information to target cells. For the last decade, the interest in EV research has exponentially increased though thorough studies of their roles in various pathologies that was not previously possible due to technical limitations...
June 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28668886/an-alpha-kinase-2-gene-variant-disrupts-filamentous-actin-localization-in-the-surface-cells-of-colorectal-cancer-spheroids
#18
Kensuke Nishi, Hao Luo, Kazuhiko Nakabayashi, Keiko Doi, Shuhei Ishikura, Yuri Iwaihara, Yasuhiro Yoshida, Kumpei Tanisawa, Tomio Arai, Seijiro Mori, Motoji Sawabe, Masaaki Muramatsu, Masashi Tanaka, Toshifumi Sakata, Senji Shirasawa, Toshiyuki Tsunoda
BACKGROUND/AIM: Alpha-kinase 2 (ALPK2), suggested to be a novel tumour-suppressor gene down-regulated by oncogenic KRAS, plays a pivotal role in luminal apoptosis in normal colonic crypts. The aim of this study was to determine the association between ALPK2 germline variants and colorectal cancer. MATERIALS AND METHODS: Missense single nucleotide variants in the exons of the ALPK2 gene in 2,343 consecutive autopsy cases (1,446 cases with cancer and 897 cases without cancer) were screened using HumanExome BeadChip arrays...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28668883/apremilast-induces-apoptosis-of-human-colorectal-cancer-cells-with-mutant-kras
#19
Kensuke Nishi, Hao Luo, Shuhei Ishikura, Keiko Doi, Yuri Iwaihara, Lauren Wills, George S Baillie, Toshifumi Sakata, Senji Shirasawa, Toshiyuki Tsunoda
BACKGROUND/AIM: We previously reported the crucial roles of oncogenic Kirsten rat sarcoma viral oncogene homologue (KRAS) in inhibiting apoptosis and disrupting cell polarity via the regulation of phosphodiesterase type 4B2 (PDE4B2) expression in human colorectal cancer (CRC) HCT116 cells in a three-dimensional culture (3DC). Here, we evaluated the effects of apremilast, a selective PDE4 inhibitor, on luminal apoptosis in 3DC and nude mice assay using HKe3 human CRC cells stably expressing wild-type (wt)PDE4B2 (HKe3-wtPDE4B2), mutant (mt)PDE4B2 (kinase dead) (HKe3-wtKRAS), wtKRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS)...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28667794/oral-administration-of-polaprezinc-attenuates-fluorouracil-induced-intestinal-mucositis-in-a-mouse-model
#20
Zhaoyang Liu, Wenbo Xie, Mingru Li, Nan Teng, Xiao Liang, Ziqiang Zhang, Zhaogang Yang, Xiaobing Wang
5-fluorouracil (5-FU) has broadly been applied to treat colorectal cancer as one of the most effective chemotherapeutic agents. However, it frequently causes intestinal mucosal injury and related side effects, such as abdominal pain and diarrhoea, which limit the use of 5-FU in a clinic setting. Polaprezinc has gradually become known as a mucosal protective agent for the management of gastric ulcer. This study aimed to investigate the prophylactic efficacy of Polaprezinc administered orally against intestinal mucositis induced by 5-FU in mice on the condition that the anti-tumour effect could not be compromised...
July 1, 2017: Basic & Clinical Pharmacology & Toxicology
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