| 1. |
- Al-Haidari, Amr A., et al.
(författare)
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MiR-155-5p positively regulates CCL17-induced colon cancer cell migration by targeting RhoA
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:9, s. 14887-14896
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer is the second most common cause of cancer-related death, which is due to migration of tumor cells to distant sites of metastasis. Accumulating data indicate that mciroRNAs play an important role in several aspects of colon cancer cell biology. Herein, we examined the role of miR-155-5p in colon cancer cell migration induced by the CCL17-CCR4 axis in HT-29 colon cancer cells. We found that miR-155-5p knockdown in serum starved colon cancer cells decreased CCL17-induced cell chemotaxis. Moreover, knocking down miR-155-5p markedly decreased CCL17-provoked activation of RhoA in colon cancer cells. Bioinformatics analysis predicted two putative binding sites in the AU-rich element at the 3'-UTR of RhoA mRNA. MiR-155-5p binding to RhoA mRNA was verified using a target site blocker and functionally validated by RNA immunoprecipitation assays, showing that miR-155-5p-dependent regulation of RhoA mRNA is mediated by AU-rich elements present in the 3'-UTR region. Taken together, these results show that miR-155-5p positively regulates RhoA mRNA levels and translation as well as cell migration in serum starved colon cancer cells and indicate that targeting miR-155-5p might be a useful strategy to antagonize colon cancer metastasis.
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| 2. |
- Al-Haidari, Amr, et al.
(författare)
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Neutrophil extracellular traps promote surgery-induced peritoneal carcinosis of metastatic colorectal cancer via modulation of CXCR2 and αv integrin
- 2017. - Suppl 3
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 28, s. 87-88
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Konferensbidrag (refereegranskat)abstract
- Introduction: Peritoneal carcinosis (PC) is the third common site of metastatic colorectal cancer which characterized by a very low survival rate. Surgical trauma has been identified as an important factor in the progression of PC, postulated to be caused by the inflammatory response to tissue injury. The mechanism behind tumor metastasis remains poorly understood. However, existing evidence indicates that neutrophils, via Neutrophil Extracellular Traps (NETs), are implicated in the development of metastatic disease and recently identified as one of the most significant key players in promoting tumor progression. In this study, we highlight the mechanism by which NETs promote surgery-induced colon cancer cell peritoneal metastasis through regulation of key receptors, CXCR2 and αvβ3 integrin.Methods: We developed a murine model of surgical stress-induced PC by post-surgery inoculation of CT-26 murine colon cancer cell line. Surface expression of CXCR2 and αvβ3 on CT-26 cells were evaluated by flow cytometry live staining. Gene expression of extracellular matrix (ECM) proteins from wound incision wall was quantified using qRT-PCR. Function of CXCR2 and αvβ3 in tumor cell migration, proliferation, and adhesion were assessed by blocking assays using CXCR2 antagonist SB225002 and anti-CD51 in vitro and in vivo. Role of neutrophils in promoting cancer cell migration and adhesion was demonstrated using in vitro co-cultured migration and adhesion assays. NET formation was measured using modified ELISA technique of Histone-DNA complex. Depletion of NETs were achieved by daily intraperitoneal administration of 2mg/kg DNase I to mice for 10 days and tumor growth was evaluated by counting macroscopic nodules number on the peritoneum.Results: Blocking CXCR2 and Targeting αv integrin reduced tumor nodules number in vivo by 70% and 65% respectively and decreased cancer cell migration, proliferation, and adhesion in vitro. Incision wound tissue displayed pronounced reduction in ECM proteins mRNAs in treated mice with both CXCR2 antagonist and αv antibody. Mice treatment with DNase I significantly reduced tumor nodules number more than 90% compared to tumor control. Anti-CD51 decreased NET-induced CT-26 cell adhesion. Neutrophils stimulation with MIP-2 exhibits dose-dependent increase of NETosis. Co-culture of neutrophils and cancer cells provoked NETs formation and increased capacity of colon cancer cell migration while DNase I treatment abolished neutrophils NETs-induced tumor cell migration in vitroConclusion: Our novel findings implicate NETs in the development of PC due to surgical stress, suggesting that blocking NET formation might be an interesting potential therapeutic approach.
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| 4. |
- Koulaouzidis, Anastasios, et al.
(författare)
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KID Project : an internet-based digital video atlas of capsule endoscopy for research purposes
- 2017
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Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 5:6, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Capsule endoscopy (CE) has revolutionized small-bowel (SB) investigation. Computational methods can enhance diagnostic yield (DY); however, incorporating machine learning algorithms (MLAs) into CE reading is difficult as large amounts of image annotations are required for training. Current databases lack graphic annotations of pathologies and cannot be used. A novel database, KID, aims to provide a reference for research and development of medical decision support systems (MDSS) for CE.METHODS: Open-source software was used for the KID database. Clinicians contribute anonymized, annotated CE images and videos. Graphic annotations are supported by an open-access annotation tool (Ratsnake). We detail an experiment based on the KID database, examining differences in SB lesion measurement between human readers and a MLA. The Jaccard Index (JI) was used to evaluate similarity between annotations by the MLA and human readers.RESULTS: The MLA performed best in measuring lymphangiectasias with a JI of 81 ± 6 %. The other lesion types were: angioectasias (JI 64 ± 11 %), aphthae (JI 64 ± 8 %), chylous cysts (JI 70 ± 14 %), polypoid lesions (JI 75 ± 21 %), and ulcers (JI 56 ± 9 %).CONCLUSION: MLA can perform as well as human readers in the measurement of SB angioectasias in white light (WL). Automated lesion measurement is therefore feasible. KID is currently the only open-source CE database developed specifically to aid development of MDSS. Our experiment demonstrates this potential.
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| 5. |
- Nemeth, Artur, et al.
(författare)
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Capsule retention related to small bowel capsule endoscopy : a large European single-center 10-year clinical experience
- 2017
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:5, s. 677-686
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Tidskriftsartikel (refereegranskat)abstract
- Background: The most concerning complication of video capsule endoscopy (VCE) is capsule retention (CR) in the gastrointestinal (GI) tract although clinical outcome and management of patients with CR are still uncertain in a large single center material. Objectives: The aim of this retrospective study was to investigate incidence, causes, risk factors, management and clinical outcomes of CR in a large single center between 2001 and 2011. Results: 2401 consecutive small-bowel (SB) VCEs were performed. CR was detected in 25 cases (1%). CR in patients with suspected and known Crohn’s disease (CD) undergoing VCE occurred in 14/1370 (1%) including known CD 9/390 (2.3%) and suspected CD 5/980 (0.5%). CR in patients with obscure GI bleeding was observed in 11/816 (1.3%) cases. The SB was the most common site of CR with 17 cases followed by the esophagus (4 cases), colon (2 cases), and stomach (2 cases). Emergency endoscopic intervention (3 cases) and surgery (2 cases) was needed in 5 cases of CR. Elective capsule removal was performed by surgery in 6 cases and endoscopically in 8 cases. Three retained capsules dislodged after steroid treatment and another 3 cases of CR resolved without any intervention. Conclusion: This large clinical material demonstrates that CR is a rare complication with a favorable clinical outcome. Most patients with CR can be electively managed with non-surgical intervention.
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| 6. |
- Sternby, Hanna, et al.
(författare)
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IL-6 and CRP are superior in early differentiation between mild and non-mild acute pancreatitis
- 2017
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 17:4, s. 550-554
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Tidskriftsartikel (refereegranskat)abstract
- Background The revised Atlanta classification on acute pancreatitis (AP) presents distinct criteria for severity categorization. Due to the lack of reliable prognostic markers, a majority of patients with AP are currently hospitalized and initially managed identically. As incidence and financial costs are rising the need for early severity differentiation will increase. This study aimed to investigate the capacity of biomarkers to stratify AP patients during the initial course of the disease. Methods Patients with AP were prospectively enrolled and dichotomized into mild or non-mild (moderately severe and severe AP) according to the revised Atlanta classification. Serum samples taken within 13–36 h after onset of disease were analyzed for 20 biomarkers. Through receiver operating curves cut-off levels were set for 5 biomarkers whose stratifying ability was further analyzed. Additionally, the patients were classified according to the harmless acute pancreatitis score (HAPS). Results Among the 175 patients, 70.9% had mild and 29.1% non-mild AP. CRP and IL-6 combined, with cut-off levels 57.0 and 23.6 respectively, demonstrated superior discriminative capacity with an area under the curve of 0.803, sensitivity 98%, specificity 54% and a positive and negative likelihood ratio of 2.1 and 0.06 for the non-mild group. Regarding the mild group likelihood ratios were positive 26.5 and negative 0.48. The identification potential of the HAPS was generally inferior when compared to CRP plus IL-6. Conclusions In this study CRP and IL-6 demonstrate a clinically relevant capacity to differentiate mild from non-mild AP early in the course of AP.
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| 7. |
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| 8. |
- Thorlacius, Henrik, et al.
(författare)
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Serrated polyps–a concealed but prevalent precursor of colorectal cancer
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:6-7, s. 654-661
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Forskningsöversikt (refereegranskat)abstract
- Serrated polyps have long been considered to lack malignant potential but accumulating data suggest that these lesions may cause up to one-third of all sporadic colorectal cancer. Serrated polyps are classified into three subtypes, including sessile serrated adenomas/polyps (SSA/Ps), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). SSA/P and TSA harbour malignant potential but TSA represents only 1–2%, wheras SSA/P constitute up to 20% of all serrated lesions. HPs are most common (80%) of all serrated polyps but are considered to have a low potential of developing colorectal cancer. Due to their subtle appearence, detection and removal of serrated polyps pose a major challenge to endoscopists. Considering that precancerous serrated polyps are predominately located in the right colon could explain why interval cancers most frequently appear in the proximal colon and why colonoscopy is less protective against colon cancer in the proximal compared to the distal colon. Despite the significant impact on colorectal cancer incidence, the aetiology, incidence, prevalence, and natural history of serrated polyps is incompletely known. To effectively detect, remove, and follow-up serrated polyps, endoscopists and pathologists should be well-informed about serrated polyps. This review highlights colorectal serrated polyps in terms of biology, types, diagnosis, therapy, and follow-up.
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| 9. |
- Toth, Ervin, et al.
(författare)
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Colonic obstruction caused by video capsule entrapment in a metal stent
- 2017
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Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- Video capsule endoscopy (VCE) has become the method of choice for visualizing the small bowel mucosa and is generally considered to be a safe method. Although uncommon, the most feared complication of VCE is capsule retention that can potentially lead to life-threatening bowel obstruction. Herein, we present for the first time a case of capsule retention in a colonic stent. The patient had known Crohn's disease with colonic involvement and underwent an uneventful but incomplete small bowel VCE for assessment of disease activity and extension for optimizing medical treatment. Five months later, the patient presented with intestinal obstruction due to a Crohn's-stricture in the sigmoid colon, which was successfully decompressed with a self-expandable metal stent. Nonetheless, two days later the patient showed signs of bowel obstruction again and abdominal X-ray showed that the capsule was trapped in the metal stent in the sigmoid colon. Subsequently, emergency surgery was performed and the patient fully recovered. Intestinal capsule retention necessitating interventional removal is rare. This report describes a unique case of capsule retention in a colonic metal stent and highlights the potential risk of performing capsule endoscopy examinations in patients with gastrointestinal stents.
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| 10. |
- Toth, Ervin, et al.
(författare)
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Video capsule colonoscopy in routine clinical practice
- 2017
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Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colon capsule endoscopy (CCE) offers direct mucosal visualisation without sedation or gas insufflation required in conventional colonoscopy (CC). However, evidence for the role of CCE as an adjunct or alternative to CC remains equivocal. In this observational cohort study, we report our experience of using CCE to investigate patients with suspected colon pathology at a tertiary referral centre. Methods: From 2007-2015, consecutive patients requiring colonoscopy were recruited from a tertiary care centre in Malmo, Sweden. Data collected: patient demographics, indication for CCE, findings, bowel cleansing, colon transit time (CTT) and completeness of colon examination. Results: Seventy-seven patients (57 F/20 F, median age 56 years) were included. The reason for CCE was previously incomplete or refused CC in 39 and 26 cases, and follow up of previous findings in 12 cases, respectively. The main clinical indications were gastrointestinal (GI) bleeding (n=28; 36%) and suspected inflammatory bowel disease (IBD) or follow-up of known IBD (n=23; 30%). CCE was complete in 58/77 (75%) patients. In 3 patients the colon was not reached; in the other 16, the capsule reached the rectum (n=4), sigmoid (n=6), descending colon (n=5) and transverse colon (n=1). Findings were: normal CCE (n=15; 19%) colonic diverticula (n=29; 38%), polyps (n=17; 22%), active IBD (n=12; 16%), haemorrhoids (n=8; 10%), colonic angioectasia (n=4; 5%) and cancer (n=1; 1%). Small-bowel findings were recorded in 8 (10%) patients. All patients tolerated bowel preparation and CCE well. Two patients with an ulcerated small-bowel stricture and cancer respectively experienced temporary capsule retention with spontaneous resolution. Conclusions: CCE is a well-tolerated alternative to CC, but requires technological improvement and optimisation of clinical practice to meet current reference standards. Although further technical development is required, CCE may complement or even replace CC for certain clinical indications.
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