| 11. |
|
|
| 12. |
- Al-Haidari, Amr, et al.
(författare)
-
MiR-155-5p controls colon cancer cell migration via post-transcriptional regulation of Human Antigen R (HuR)
- 2018
-
Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835. ; 421, s. 145-151
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR. Bioinformatics analysis predicted two putative binding sites in the AU-rich elements (AREs) at the 3′-UTR of HuR mRNA. MiR-155-5p binding to HuR was verified using specific target site blockers and functionally validated by use of RNA immunoprecipitation assays, showing that miR-155-5p-dependent regulation of HuR expression is mediated by AREs. Targeting AREs with a specific blocker inhibited colon cancer cell migration. Taken together, these novel findings demonstrate that AREs mediate miR-155-5p positive regulation of HuR mRNA levels and translation as well as migration in colon cancer cells, suggesting that targeting miR-155-5p and/or Hur might be useful therapeutic strategies against colon cancer metastasis.
|
|
| 13. |
- Al-Haidari, Amr, et al.
(författare)
-
Neutrophil extracellular traps promote surgery-induced peritoneal carcinosis of metastatic colorectal cancer via modulation of CXCR2 and αv integrin
- 2017. - Suppl 3
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 28, s. 87-88
-
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.
|
|
| 14. |
- Algaber, Anwar, et al.
(författare)
-
MicroRNA-340-5p inhibits colon cancer cell migration via targeting of RhoA
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 16934-16934
-
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.
|
|
| 15. |
|
|
| 16. |
- Arthursson, Victoria, et al.
(författare)
-
Risk of recurrence after endoscopic resection of nonpedunculated T1 colorectal cancer
- 2022
-
Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X. ; 54:11, s. 1071-1077
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The long-term outcome after local excision of T1 colorectal cancer (CRC) remains unknown. The aim of this study was to examine clinical and histopathological risk factors for recurrence in patients with T1 CRC undergoing endoscopic resection.METHODS: This was a retrospective registry-based population study on prospectively collected data of all patients with nonpedunculated T1 CRC undergoing only local excision (no salvage surgery) in Sweden between 2009 and 2018. Potential risk factors for recurrence, including age, sex, tumor location, resection margins, lymphovascular, perineural, and submucosal invasion, grade of differentiation, and mucinous subtype, were analyzed using univariate and multivariate cox regression.RESULTS: Median follow-up time was 60 months, and 28 /602 patients (4.7 %) had a recurrence (13 local and 18 distant). Recurrence rate stratified by submucosal invasion was: Sm1 3.5 % (14 /397), Sm2 6.0 % (8 /133), and Sm3 8.3 % (6 /72), with no significant differences. Resection margins, lymphovascular and perineural invasion, grade of differentiation, mucinous subtype, and age were not significant risk factors for recurrence. In contrast, rectal location was found to be a significant risk factor for tumor recurrence in multivariate analysis (hazard ratio 3.08, P = 0.006). The 3- and 5-year disease-free survival was 96.2 % and 91.1 %, respectively, in T1 CRC patients undergoing endoscopic resection.CONCLUSION: Tumor recurrence was rare (4.7 %) in this large population-based study on recurrence after local excision of nonpedunculated T1 CRC. Rectal location was an independent risk factor for recurrence, suggesting the need for strict surveillance after endoscopic resection of early rectal cancer.
|
|
| 17. |
- Asaduzzaman, Muhammad, et al.
(författare)
-
Critical role of p38 mitogen-activated protein kinase signaling in septic lung injury.
- 2008
-
Ingår i: Critical Care Medicine. - 1530-0293. ; 36:2, s. 482-488
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Leukocyte-mediated tissue damage is a key feature in septic lung injury, although the signaling mechanisms behind pulmonary recruitment of leukocytes remain elusive. The aim of the present study was to define the role of p38 mitogen-activated protein kinase (MAPK) signaling in septic lung injury. DESIGN: Prospective experimental study. SETTING: University hospital research unit. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Pulmonary edema, bronchoalveolar infiltration of leukocytes, levels of myeloperoxidase, and CXC chemokines were determined 6 and 24 hrs after cecal ligation and puncture (CLP). The specific p38 MAPK inhibitors SB 239063 and SKF 86002 were given immediately before CLP induction. Phosphorylation and activity of p38 MAPK were determined by immunoprecipitation and Western blot. MEASUREMENTS AND MAIN RESULTS: CLP induced clear-cut pulmonary damage characterized by edema formation, leukocyte infiltration, and increased levels of CXC chemokines in the lung. Moreover, CLP increased phosphorylation and activity of p38 MAPK in the lung, which was markedly inhibited by SB 239063. Interestingly, inhibition of p38 MAPK signaling protected against CLP-induced lung damage and edema. Indeed, both SB 239063 and SKF 86002 decreased CLP-induced leukocyte recruitment in the bronchoalveolar space and formation of CXC chemokines in the lung. CONCLUSIONS: Our data demonstrate that p38 MAPK signaling constitutes a key role in regulating CXC chemokine production in septic lung injury and that inhibition of p38 MAPK activity abolishes pulmonary infiltration of leukocytes as well as lung edema. These novel findings suggest that targeting the p38 MAPK signaling pathway may pave the way for a new therapeutic strategy against lung injury in polymicrobial sepsis.
|
|
| 18. |
- Asaduzzaman, Muhammad, et al.
(författare)
-
LFA-1 AND MAC-1 MEDIATE PULMONARY RECRUITMENT OF NEUTROPHILS AND TISSUE DAMAGE IN ABDOMINAL SEPSIS.
- 2008
-
Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1540-0514 .- 1073-2322. ; 30, s. 254-259
-
Tidskriftsartikel (refereegranskat)abstract
- Neutrophil-mediated lung damage is an insidious feature in septic patients, although the adhesive mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. The aim of the present study was to define the role of lymphocyte function-antigen 1 (LFA-1) and membrane-activated complex 1 (Mac-1) in septic lung injury. Pulmonary edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, and CXC chemokines were determined after cecal ligation and puncture (CLP). Mice were treated with monoclonal antibodies directed against LFA-1 and Mac-1 before CLP induction. Cecal ligation and puncture induced clear-cut pulmonary damage characterized by edema formation, neutrophil infiltration, and increased levels of CXC chemokines in the lung. Notably, immunoneutralization of LFA-1 or Mac-1 decreased CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 64%. Moreover, functional inhibition of LFA-1 and Mac-1 abolished CLP-induced lung damage and edema. However, formation of CXC chemokines in the lung was intact in mice pretreated with the anti-LFA-1 and anti-Mac-1 antibodies. Our data demonstrate that both LFA-1 and Mac-1 regulate pulmonary infiltration of neutrophils and lung edema associated with abdominal sepsis. Thus, these novel findings suggest that LFA-1 or Mac-1 may serve as targets to protect against lung injury in polymicrobial sepsis.
|
|
| 19. |
- Aurin, Johanna, et al.
(författare)
-
Age at first childbirth and breast cancer survival : A prospective cohort study
- 2020
-
Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 13:1
-
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.
|
|
| 20. |
- Awla, Darbaz, et al.
(författare)
-
Lymphocyte function antigen-1 regulates neutrophil recruitment and tissue damage in acute pancreatitis.
- 2011
-
Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 163, s. 413-423
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Leucocyte infiltration is a rate-limiting step in the pathophysiology of acute pancreatitis (AP) although the adhesive mechanisms supporting leucocyte-endothelium interactions in the pancreas remain elusive. The aim of this study was to define the role of lymphocyte function antigen-1 (LFA-1) in regulating neutrophil-endothelium interactions and tissue damage in severe AP. Experimental approach: Pancreatitis was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in mice. LFA-1 gene-targeted mice and an antibody directed against LFA-1 were used to define the role of LFA-1. Key results: Taurocholate challenge caused a clear-cut increase in serum amylase, neutrophil infiltration, CXCL2 (macrophage inflammatory protein-2) formation, trypsinogen activation and tissue damage in the pancreas. Inhibition of LFA-1 function markedly reduced taurocholate-induced amylase levels, accumulation of neutrophils, production of CXC chemokines and tissue damage in the pancreas. Notably, intravital microscopy revealed that inhibition of LFA-1 abolished taurocholate-induced leucocyte adhesion in postcapillray venules of the pancreas. In addition, pulmonary infiltration of neutrophils was attenuated by inhibition of LFA-1 in mice challenged with taurocholate. However, interference with LFA-1 had no effect on taurocholate-induced activation of trypsinogen in the pancreas. Conclusions and Implications: Our novel data suggest that LFA-1 plays a key role in regulating neutrophil recruitment, CXCL2 formation and tissue injury in the pancreas. Moreover, these results suggest that LFA-1-mediated inflammation is a downstream component of trypsinogen activation in the pathophysiology of AP. Thus, we conclude that targeting LFA-1 may be a useful approach to protect against pathological inflammation in the pancreas.
|
|
