| 1. |
- Algaber, Anwar, et al.
(författare)
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MicroRNA-340-5p inhibits colon cancer cell migration via targeting of RhoA
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 16934-16934
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Tidskriftsartikel (refereegranskat)abstract
- Colon cancer is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the most insidious aspect of cancer progression. Convincing data suggest that microRNAs (miRs) play a key function in colon cancer biology. We examined the role of miR-340-5p in regulating RhoA expression as well as cell migration and invasion in colon cancer cells. Levels of miR-340-5p and RhoA mRNA varied inversely in serum-free and serum-grown HT-29 and AZ-97 colon cancer cells. It was found transfection with miR-340-5p not only decreased expression of RhoA mRNA and protein levels in HT-29 cells but also reduced colon cancer cell migration and invasion. Bioinformatics analysis predicted one putative binding sites at the 3'-UTR of RhoA mRNA. Targeting this binding site with a specific blocker reversed mimic miR-340-5p-induced inhibition of RhoA activation and colon cancer cell migration and invasion. These novel results suggest that miR-340-5p is an important regulator of colon cancer cell motility via targeting of RhoA and further experiments are warranted to evaluate the role of miR-340-5p in colon cancer metastasis.
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| 2. |
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| 3. |
- Aurin, Johanna, et al.
(författare)
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Age at first childbirth and breast cancer survival : A prospective cohort study
- 2020
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Late age at first childbirth is a well-established risk factor for breast cancer. Previous studies have, however, shown conflicting results to whether late age at first childbirth also influences the prognosis of breast cancer survival. The aim of this study was to examine age at first birth in relation to survival after breast cancer diagnosis. Results: We used information from the Malmö Diet and Cancer study. At baseline 17,035 women were included. All women were followed from the year they developed breast cancer until they either died or until the end of follow-up. All women were asked how many children they had given birth to and were then divided into different groups, ≤ 20, > 20 to ≤ 25, > 25 to ≤ 30 and > 30. Nulliparous women form a separate group. Survival analyses were then performed using Cox proportional hazard survival analysis. Women in all age groups had a lower risk of breast cancer specific death as compared to the reference group ≤ 20, however non-significantly. Nulliparous women had a higher risk of breast cancer specific death as compared to the same reference group, however these results were not statistically significant. We could not see any negative effect of late first childbirth on breast cancer specific survival.
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| 4. |
- Cadoni, Sergio, et al.
(författare)
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Water-assisted colonoscopy: an international modified Delphi review on definitions and practice recommendations
- 2021
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Ingår i: Gastrointestinal Endoscopy. - : Elsevier BV. - 1097-6779 .- 0016-5107. ; 93:6, s. 1411-1420
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Since 2008, a plethora of research studies has compared the efficacy of water-assisted (aided) colonoscopy (WAC) and underwater resection (UWR) of colorectal lesions with standard colonoscopy. We reviewed and graded the research evidence with potential clinical application. We conducted a modified Delphi consensus among experienced colonoscopists on definitions and practice of water immersion (WI), water exchange (WE), and UWR. Methods: Major databases were searched to obtain research reports that could potentially shape clinical practice related to WAC and UWR. Pertinent references were graded (Grading of Recommendations, Assessment, Development and Evaluation). Extracted data supporting evidence-based statements were tabulated and provided to respondents. We received responses from 55 (85% surveyed) experienced colonoscopists (37 experts and 18 nonexperts in WAC) from 16 countries in 3 rounds. Voting was conducted anonymously in the second and third round, with ≥80% agreement defined as consensus. We aimed to obtain consensus in all statements. Results: In the first and the second modified Delphi rounds, 20 proposed statements were decreased to 14 and then 11 statements. After the third round, the combined responses from all respondents depicted the consensus in 11 statements (S): definitions of WI (S1) and WE (S2), procedural features (S3-S5), impact on bowel cleanliness (S6), adenoma detection (S7), pain score (S8), and UWR (S9-S11). Conclusions: The most important consensus statements are that WI and WE are not the same in implementation and outcomes. Because studies that could potentially shape clinical practice of WAC and UWR were chosen for review, this modified Delphi consensus supports recommendations for the use of WAC in clinical practice. © 2020 American Society for Gastrointestinal Endoscopy
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| 5. |
- Ciuti, Gastone, et al.
(författare)
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Frontiers of robotic colonoscopy : A comprehensive review of robotic colonoscopes and technologies
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:6
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Forskningsöversikt (refereegranskat)abstract
- Flexible colonoscopy remains the prime mean of screening for colorectal cancer (CRC) and the gold standard of all population-based screening pathways around the world. Almost 60% of CRC deaths could be prevented with screening. However, colonoscopy attendance rates are affected by discomfort, fear of pain and embarrassment or loss of control during the procedure. Moreover, the emergence and global thread of new communicable diseases might seriously affect the functioning of contemporary centres performing gastrointestinal endoscopy. Innovative solutions are needed: artificial intelligence (AI) and physical robotics will drastically contribute for the future of the healthcare services. The translation of robotic technologies from traditional surgery to minimally invasive endoscopic interventions is an emerging field, mainly challenged by the tough requirements for miniaturization. Pioneering approaches for robotic colonoscopy have been reported in the nineties, with the appearance of inchworm-like devices. Since then, robotic colonoscopes with assistive functionalities have become commercially available. Research prototypes promise enhanced accessibility and flexibility for future therapeutic interventions, even via autonomous or robotic-assisted agents, such as robotic capsules. Furthermore, the pairing of such endoscopic systems with AI-enabled image analysis and recognition methods promises enhanced diagnostic yield. By assembling a multidisciplinary team of engineers and endoscopists, the paper aims to provide a contemporary and highly-pictorial critical review for robotic colonoscopes, hence providing clinicians and researchers with a glimpse of the major changes and challenges that lie ahead.
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| 6. |
- Ding, Zhiyi, et al.
(författare)
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Targeting s100a9 reduces neutrophil recruitment, inflammation and lung damage in abdominal sepsis
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:23
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Tidskriftsartikel (refereegranskat)abstract
- S100A9, a pro-inflammatory alarmin, is up-regulated in inflamed tissues. However, the role of S100A9 in regulating neutrophil activation, inflammation and lung damage in sepsis is not known. Herein, we hypothesized that blocking S100A9 function may attenuate neutrophil recruitment in septic lung injury. Male C57BL/6 mice were pretreated with the S100A9 inhibitor ABR-238901 (10 mg/kg), prior to cercal ligation and puncture (CLP). Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested for analysis of neutrophil infiltration as well as edema and CXC chemokine production. Blood was collected for analysis of membrane-activated complex-1 (Mac-1) expression on neutrophils as well as CXC chemokines and IL-6 in plasma. Induction of CLP mark-edly increased plasma levels of S100A9. ABR-238901 decreased CLP-induced neutrophil infiltration and edema formation in the lung. In addition, inhibition of S100A9 decreased the CLP-induced up-regulation of Mac-1 on neutrophils. Administration of ABR-238901 also inhibited the CLP-induced increase of CXCL-1, CXCL-2 and IL-6 in plasma and lungs. Our results suggest that S100A9 promotes neutrophil activation and pulmonary accumulation in sepsis. Targeting S100A9 function decreased formation of CXC chemokines in circulation and lungs and attenuated sepsis-induced lung damage. These novel findings suggest that S1000A9 plays an important pro-inflammatory role in sepsis and could be a useful target to protect against the excessive inflammation and lung damage associated with the disease.
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| 7. |
- Khan, Umama, et al.
(författare)
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Neutrophil extracellular traps in colorectal cancer progression and metastasis
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:14
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Forskningsöversikt (refereegranskat)abstract
- Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.
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| 8. |
- Lepsenyi, Mattias, et al.
(författare)
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CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
- 2021
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Ingår i: Clinical and Experimental Metastasis. - : Springer Science and Business Media LLC. - 1573-7276 .- 0262-0898. ; 38:4, s. 401-410
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Tidskriftsartikel (refereegranskat)abstract
- Peritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.
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| 9. |
- Linders, Johan, et al.
(författare)
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Extracellular cold-inducible RNA-binding protein regulates neutrophil extracellular trap formation and tissue damage in acute pancreatitis
- 2020
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 0023-6837. ; 100:12, s. 1618-1630
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil extracellular traps (NETs) play a key role in the development of acute pancreatitis (AP). In the present study, we studied the role of extracellular cold-inducible RNA-binding protein (eCIRP), a novel damage-associated-molecular-pattern molecule, in severe AP. C57BL/6 mice underwent retrograde infusion of taurocholate into the pancreatic duct. C23, an eCIRP inhibitor, was given 1 h prior to induction of AP. Pancreatic, lung, and blood samples were collected and levels of citrullinated histone 3, DNA-histone complexes, eCIRP, myeloperoxidase (MPO), amylase, cytokines, matrix metalloproteinase-9 (MMP-9), and CXC chemokines were quantified after 24 h. NETs were detected by electron microscopy in the pancreas and bone marrow-derived neutrophils. Amylase secretion was analyzed in isolated acinar cells. Plasma was obtained from healthy individuals and patients with mild and moderate severe or severe AP. Taurocholate infusion induced NET formation, inflammation, and tissue injury in the pancreas. Pretreatment with C23 decreased taurocholate-induced pancreatic and plasma levels of eCIRP and tissue damage in the pancreas. Blocking eCIRP reduced levels of citrullinated histone 3 and NET formation in the pancreas as well as DNA-histone complexes in the plasma. In addition, administration of C23 attenuated MPO levels in the pancreas and lung of mice exposed to taurocholate. Inhibition of eCIRP reduced pancreatic levels of CXC chemokines and plasma levels of IL-6, HMGB-1, and MMP-9 in mice with severe AP. Moreover, eCIRP was found to be bound to NETs. Coincubation with C23 reduced NET-induced amylase secretion in isolated acinar cells. Patients with severe AP had elevated plasma levels of eCIRP compared with controls. Our novel findings suggest that eCIRP is a potent regulator of NET formation in the inflamed pancreas. Moreover, these results show that targeting eCIRP with C23 inhibits inflammation and tissue damage in AP. Thus, eCIRP could serve as an effective target to attenuate pancreatic damage in patients with AP.
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| 10. |
- Rahman, Milladur, et al.
(författare)
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Transcriptomic Analysis Reveals Differential Expression of Genes between Lung Capillary and Post Capillary Venules in Abdominal Sepsis
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 22:19, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Lung endothelial cell dysfunction plays a central role in septic-induced lung injury. We hypothesized that endothelial cell subsets, capillary endothelial cells (capEC) and post capillary venules (PCV), might play different roles in regulating important pathophysiology in sepsis. In order to reveal global transcriptomic changes in endothelial cell subsets during sepsis, we induced sepsis in C57BL/6 mice by cecal ligation and puncture (CLP). We confirmed that CLP induced systemic and lung inflammation in our model. Endothelial cells (ECs) from lung capillary and PCV were isolated by cell sorting and transcriptomic changes were analyzed by bioinformatic tools. Our analysis revealed that lung capEC are transcriptionally different than PCV. Comparison of top differentially expressed genes (DEGs) of capEC and PCV revealed that capEC responses are different than PCV during sepsis. It was found that capEC are more enriched with genes related to regulation of coagulation, vascular permeability, wound healing and lipid metabolic processes after sepsis. In contrast, PCV are more enriched with genes related to chemotaxis, cell–cell adhesion by integrins, chemokine biosynthesis, regulation of actin filament process and neutrophil homeostasis after sepsis. In addition, we predicted some transcription factor targets that regulate a significant number of DEGs in sepsis. We proposed that targeting certain DEGs or transcriptional factors would be useful in protecting against sepsis-induced lung damage
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