| 1. |
- 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.
|
|
| 2. |
|
|
| 3. |
- Madhi, Raed, et al.
(författare)
-
c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis
- 2019
-
Ingår i: Journal of Leukocyte Biology. - 0741-5400. ; 106:2, s. 455-466
-
Tidskriftsartikel (refereegranskat)abstract
- Neutrophil extracellular traps (NETs) are involved in acute pancreatitis (AP) but mechanisms controlling NET expulsion in AP are incompletely understood. Herein, we examined the role of c-Abelson (c-Abl) kinase in NET formation and tissue damage in severe AP. AP was induced by taurocholate infusion into pancreatic duct or intraperitoneal administration of l-arginine in mice. Pancreatic, lung, and blood samples were collected and levels of phosphorylated c-Abl kinase, citrullinated histone 3, DNA-histone complexes, myeloperoxidase, amylase, cytokines, and CXC chemokines were quantified. Citrullinated histone 3, reactive oxygen species (ROS), and NET formation were determined in bone marrow neutrophils. Taurocholate challenge increased phosphorylation of c-Abl kinase and levels of citrullinated histone 3 in the pancreas as well as DNA-histone complexes in the plasma. Administration of the c-Abl kinase inhibitor GZD824 not only abolished activation of c-Abl kinase but also decreased levels of citrullinated histone 3 in the pancreas and DNA-histone complexes in the plasma of animals with AP. Moreover, GZD824 decreased plasma levels of amylase, IL-6, and MMP-9 as well as edema, acinar cell necrosis, hemorrhage, CXC chemokine formation, and neutrophil infiltration in the inflamed pancreas. A beneficial effect of c-Abl kinase inhibition was confirmed in l-arginine-induced pancreatitis. In vitro, inhibition of c-Abl kinase reduced TNF-α-induced formation of ROS, histone 3 citrullination, and NETs in isolated bone marrow neutrophils. Our findings demonstrate that c-Abl kinase regulates NET formation in the inflamed pancreas. In addition, inhibition of c-Abl kinase reduced pancreatic tissue inflammation, and damage in AP. Thus, targeting c-Abl kinase might be a useful way to protect the pancreas in severe AP.
|
|
| 4. |
- Madhi, Raed, et al.
(författare)
-
Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis
- 2019
-
Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 234:7, s. 11850-11860
-
Tidskriftsartikel (refereegranskat)abstract
- Recent evidence suggests that neutrophil extracellular traps (NETs) play an important role in the development of acute pancreatitis (AP). Herein, we examined the role of peptidylarginine deiminase (PAD), which has been shown to regulate NET formation, in severe AP. AP was induced by retrograde of taurocholate infusion into pancreatic duct in C57BL/6 mice. PAD was pharmacologically inhibited using Cl-amidine, a pan-PAD inhibitor. Pancreata were collected, and histones, citrullinated histone 3, chemokines, myeloperoxidase, and NETs were quantified. Chemokines, matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and DNA-histone complexes were determined in plasma samples. Infusion of taurocholate induced formation of NETs in pancreatic tissues of mice. Pretreatment with Cl-amidine markedly reduced the NET formation in the inflamed pancreas. Moreover, inhibition of PAD decreased the levels of blood amylase as well as edema, acinar cell necrosis, hemorrhage, and neutrophil infiltration in the pancreas of animals with AP. Administration of Cl-amidine attenuated the myeloperoxidase levels in the pancreas and lung of mice exposed to taurocholate. In addition, Cl-amidine decreased pancreatic levels of CXC chemokines, plasma levels of IL-6, and MMP-9 in mice with severe AP. This study shows that Cl-amidine is a potent inhibitor of NET formation in severe AP. Also, our results suggest that PAD regulates pathological inflammation and tissue damage in the inflamed pancreas. Thus, targeting PAD might be a useful strategy to treat patients with severe AP.
|
|
| 5. |
- Nilsson, Emelie, et al.
(författare)
-
Use of Oral Contraceptives and Breast Cancer Survival
- 2016
-
Ingår i: International Journal of Womens Health and Wellness. - : ClinMed International Library. - 2474-1353. ; 2:4
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Oral contraceptives (OC) have been shown to give a transient increased breast cancer risk. However, studies on breast cancer survival after OC use are sparse and conflicting.Aim: The aim of this study was to examine previous use of OC in relation to survival after breast cancer diagnosis.Methods: Data was collected from Malmö Diet and Cancer Study, with baseline examinations between 1991 and 1996. Out of 17035 women who completed all study parts, 765 women with incident breast cancer were included in this study. Kaplan Meier and Cox Proportional Hazards analyses, with 95% confidence intervals (CI), were used to study OC in relation to breast cancer-specific and overall survival. All analyses were stratified on age at diagnosis.Results: Women who had ever used OC were younger and more often had grade III tumors than those who had never used OC. Breast cancer-specific survival in women who ever had used OC was better when adjusting for BMI, socioeconomic status as well as tumor characteristics. However, when adjusting for age at diagnosis, the results did not remain significant (0.68, CI 95% 0.39- 1.18). Stratified analyses on age at diagnosis (40-55, 56-70 and ≥ 71) showed no statistically significant associations.Conclusion: In this study we could not demonstrate a significant effect of OC use on breast cancer survival.
|
|
| 6. |
- Rönnow, Carl-Fredrik, et al.
(författare)
-
Endoscopic submucosal dissection of 301 large colorectal neoplasias : outcome and learning curve from a specialized center in Europe
- 2018
-
Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 6:11, s. 1340-1348
-
Tidskriftsartikel (refereegranskat)abstract
- Background and study aims Endoscopic submucosal dissection (ESD) allows en bloc resection of large colorectal lesions but ESD experience is limited outside Asia. This study evaluated implementation of ESD in the treatment of colorectal neoplasia in a Western center. Patients and methods Three hundred and one cases of colorectal ESD (173 rectal and 128 colonic lesions) were retrospectively evaluated in terms of outcome, learning curve and complications. Results Median size was 4 cm (range 1 - 12.5). En bloc resection was achieved in 241 cases amounting to an en bloc resection rate of 80 %. R0 resection was accomplished in 207 cases (69 %), RX and R1 were attained in 83 (27 %) and 11 (4 %) cases, respectively. Median time was 98 min (range 10 - 588) and median proficiency was 7.2 cm 2 /h. Complications occurred in 24 patients (8 %) divided into 12 immediate perforations, five delayed perforations, one immediate bleeding and six delayed bleedings. Six patients (2 %), all with proximal lesions, had emergency surgery. Two hundred and four patients were followed up endoscopically and median follow-up time was 13 months (range 3 - 53) revealing seven recurrences (3 %). En bloc rate improved gradually from 60 % during the first period to 98 % during the last period. ESD proficiency significantly improved between the first study period (3.6 cm 2 /h) and the last study period (10.8 cm 2 /h). Conclusions This study represents the largest material on colorectal ESD in the west and shows that colorectal ESD can be implemented in clinical routine in western countries after appropriate training and achieve a high rate of en bloc and R0 resection with a concomitant low incidence of complications. ESD of proximal colonic lesions should be attempted with caution during the learning curve because of higher risk of complications.
|
|
| 7. |
- Rönnow, Carl-Fredrik, et al.
(författare)
-
Endoscopic submucosal dissection of malignant non-pedunculated colorectal lesions
- 2018
-
Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 6:8, s. 961-968
-
Tidskriftsartikel (refereegranskat)abstract
- Background and study aimsEndoscopic submucosal dissection (ESD) is an established method for en bloc resection of large non-pedunculated colorectal lesions in Asia but dissemination of ESD in Western countries is limited. The aim of this study was to evaluate the role of ESD in the management of malignant non-pedunculated colorectal lesions in a European center.Patients and methods Among 255 patients undergoing colorectal ESD between 2014 and 2016, 29 cases were identified as submucosal invasive cancers and included in this study. The main outcomes were en bloc, R0 and curative resection as well as procedural time, complications and recurrence.Results Median tumor size was 40 mm (range 20 – 70 mm). Thirteen cancers were located in the colon and 16 were located in the rectum. Procedural time was 89 minutes (range 18 – 594 minutes). Complete resection was achieved in 28 cases, en bloc and R0 resection rates were 83 % and 69 %, respectively. Curative resection rate was 38 %. One case had a perforation in the sigmoid colon requiring emergency surgery. No significant bleeding occurred. Six patients underwent additional surgery after ESD, one of whom had residual tumor. One recurrence was detected in 20 patients that were followed-up endoscopically, median follow-up time was 13 months (range 2 – 30 months).Conclusion ESD seems to be a safe and effective method for treating non-pedunculated malignant colorectal lesions after careful patient selection and proper endoscopic training.
|
|
| 8. |
- Rönnow, Carl Fredrik, et al.
(författare)
-
Forceps Biopsies Are Not Reliable in the Workup of Large Colorectal Lesions Referred for Endoscopic Resection : Should They Be Abandoned?
- 2019
-
Ingår i: Diseases of the Colon and Rectum. - 0012-3706. ; 62:9, s. 1063-1070
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Biopsies are routinely obtained in the workup of large colorectal polyps before endoscopic resection. OBJECTIVE: This study aimed to examine how reliable biopsies are in terms of reflecting the true histopathology of large colorectal polyps, in the clinical routine. DESIGN: This is a retrospective study. SETTINGS: Data from patients undergoing polypectomy of large colorectal polyps at the endoscopy unit, Skåne University Hospital Malmö, between January 2014 and December 2016 were scrutinized. PATIENTS: A total of 485 colorectal lesions were biopsied within 1 year before complete endoscopic removal. Biopsy-obtained specimens were compared with completely resected specimens in terms of concordance and discordance and if the final result was upgraded or downgraded. MAIN OUTCOME MEASURES: The primary outcome measured was the concordance between biopsy-obtained specimens and completely resected specimens. RESULTS: Median lesion size was 3 cm (range 1-11). In 189 cases (39%), biopsies did not provide a correct dysplastic grade compared with final pathology after complete resection. One hundred forty-three cases (29%) and 46 cases (9%) were upgraded and downgraded. The percentage of cases with discordant biopsy results was 40% in cases with 1 biopsy taken and 38% in cases where multiple biopsies had been sampled. Time from biopsy to complete resection did not influence the erroneous outcome of biopsies. Notably, the percentage of discordant biopsy results was 37% and 35% in lesions measuring 1 to 2 cm and 2 to 4 cm. However, this percentage increased to 48% in colorectal lesions larger than 4 cm. LIMITATIONS: This study was designed to reflect the clinical routine, the number of biopsies obtained and forceps technique were hence not standardized, which constitutes a limitation. CONCLUSIONS: This study demonstrates that cancer-negative forceps biopsies of large colorectal polyps, referred for endoscopic resection, are not reliable. Considering that endoscopic resection of lesions containing superficial cancer is plausible, the clinical value of forceps biopsies in lesions suitable for endoscopic resection is questionable. See Video Abstract at http://links.lww.com/DCR/A984. LAS BIOPSIAS CON FÓRCEPS NO SON CONFIABLES EN EL ESTUDIO DE LAS LESIONES COLORRECTALES GRANDES REFERIDAS PARA RESECCIÓN ENDOSCÓPICA: ¿DEBERÍAN ABANDONARSE?: Las biopsias se obtienen de forma rutinaria en el estudio de pólipos colorrectales grandes previo a resección endoscópica. OBJETIVO: Analizar que tan confiables son las biopsias en cuanto a reflejar la verdadera histopatología de los pólipos colorrectales grandes, en la rutina clínica. DISEÑO:: Este es un estudio retrospectivo. AJUSTES: Los datos de pacientes sometidos a polipectomía de pólipos colorrectales grandes en la unidad de endoscopia, en Skåne University Hospital Malmö, entre enero de 2014 y diciembre de 2016 fueron examinados. PACIENTES: Un total de 485 lesiones colorrectales se biopsiaron dentro de un año antes de la resección endoscópica completa. Las muestras obtenidas mediante biopsia se compararon con las muestras completas resecadas en términos de concordancia y discordancia, y si el resultado final ascendió o disminuyó de categoría. PRINCIPALES MEDIDAS DE RESULTADO: Concordancia entre muestras obtenidas mediante biopsia y muestras completamente resecadas. RESULTADOS: La mediana de tamaño de lesiones fue de 3 cm (rango 1-11). En 189 casos (39%) las biopsias no proporcionaron un grado de displasia correcto en comparación con la patología final después de la resección completa. 143 casos (29%) y 46 casos (9%) ascendieron y descendieron de categoría, respectivamente. El porcentaje de casos con resultados de biopsia discordantes fue del 40% en los casos con una sola biopsia tomada y del 38% en los casos en los que se tomaron múltiples biopsias. El tiempo desde la biopsia hasta la resección completa no influyó en el resultado erróneo de las biopsias. Notablemente, el porcentaje de resultados de biopsia discordantes fue de 37% y 35% en lesiones que midieron 1-2 cm y 2-4 cm, respectivamente. Sin embargo, este porcentaje aumentó a 48% en lesiones colorrectales mayores de 4 cm. LIMITACIONES: Este estudio se diseñó para reflejar la rutina clínica, el número de biopsias obtenidas y la técnica de fórceps no fueron estandarizadas, lo que constituye una limitación. CONCLUSIONES: Este estudio demuestra que las biopsias con fórceps negativas a cáncer, de pólipos colorrectales grandes referidas para resección endoscópica, no son confiables. Teniendo en cuenta que la resección endoscópica de lesiones que contienen cáncer superficial es posible, el valor clínico de las biopsias con fórceps en lesiones aptas para la resección endoscópica es cuestionable. Vea el Resumen en video en http://links.lww.com/DCR/A984.
|
|
| 9. |
- Thorlacius, Henrik, et al.
(författare)
-
European experience of colorectal endoscopic submucosal dissection : a systematic review of clinical efficacy and safety
- 2019
-
Ingår i: Acta Oncologica. - 0284-186X. ; 58:sup1, s. 10-14
-
Forskningsöversikt (refereegranskat)abstract
- Background: Endoscopic submucosal dissection (ESD) is an advanced method allowing en bloc resection of large and complex lesions in colon and rectum. Herein, the European experience of colorectal ESD was systematically reviewed in the medical literature to determine the clinical efficacy and safety of colorectal ESD in Europe. Material and methods: A systematic search of PubMed for full-text studies including more than 20 cases of colorectal ESD emanating from European centres was performed. Data were independently extracted by two authors using predefined data fields, including efficacy and safety. Results: We included 15 studies containing a total of 1404 colorectal ESD cases (41% in the colon) performed between 2007 and 2018. Lesion size was 40 mm (range 24–59 mm) and procedure time was 102 min (range 48–176 min). En bloc resection rate was 83% (range 67–93%) and R0 resection rate was 70% (range 35–91%). Perforation rate was 7% (range 0–19%) and bleeding rate was 5% (range 0–12%). The percentage of ESD cases undergoing emergency surgery was 2% (range 0–6%). Additional elective surgery was performed in 3% of all cases due to histopathological findings showing deep submucosal invasion or more advanced cancer. The recurrence rate was 4% (range 0–12%) after a median follow-up time of 12 months (range 3–24 months). Conclusions: This review shows that ESD is effective and safe for treating large and complex colorectal lesions in Europe although there is room for improvement. Thus, it is important to develop standardized and high-quality educational programs in colorectal ESD in Europe.
|
|
| 10. |
- Thorlacius, Henrik, et al.
(författare)
-
Serrated polyps–a concealed but prevalent precursor of colorectal cancer
- 2017
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:6-7, s. 654-661
-
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.
|
|
