Advanced metastatic prostate cancer (PCa) is a fatal disease, with only palliative therapeutic options. Though almost 80% of cases of metastatic PCa present bone metastasis, our current understanding ...of the molecular mechanisms that govern this metastatic dissemination remains fragmentary. The main objective of the present study was to identify microRNA (miRNA) genes that regulate metastatic PCa.
miRNA expression profiling was done in human prostate cell lines to identify dysregulated miRNA components of advanced PCa. miR-203 expression was assessed in prostate carcinoma cell lines and clinical specimens by real-time PCR and in situ hybridization. To assess the biological significance of miR-203, miR-203 was reexpressed in bone metastatic PCa cell lines followed by in vitro and in vivo functional assays.
miR-203 expression is specifically attenuated in bone metastatic PCa suggesting a fundamental antimetastatic role for this miRNA. Reintroduction of miR-203 in bone metastatic PCa cell lines suppresses metastasis via inhibition of several critical steps of the metastatic cascade including epithelial-mesenchymal transition, invasion, and motility. Ectopic miR-203 significantly attenuated the development of metastasis in a bone metastatic model of PCa. Importantly, miR-203 regulates a cohort of pro-metastatic genes including ZEB2, Bmi, survivin, and bone-specific effectors including Runx2, a master regulator of bone metastasis.
miR-203 is an "antimetastatic" miRNA in PCa that acts at multiple steps of the PCa metastatic cascade via repression of a cohort of prometastatic targets. miR-203 may be an attractive target for therapeutic intervention in advanced PCa.
Although the incidence of inflammatory bowel disease IBD is increasing in Asia, data on long-term epidemiological trends are limited. We performed a 30-year longitudinal study to investigate temporal ...trends in the epidemiology of Crohn's disease CD and ulcerative colitis UC in Seoul, Korea.
This population-based study included 1431 IBD patients 418 CD, 1013 UC diagnosed between 1986 and 2015 in the Songpa-Kangdong district of Seoul, Korea. Temporal trends in incidence, prevalence, and disease phenotype at diagnosis were analysed.
The adjusted mean annual incidence rates of CD and UC per 100 000 inhabitants increased from 0.06 (95% confidence interval CI, 0.05-0.07) and 0.29 95% CI, 0.27-0.31, respectively, in 1986-1990 to 2.44 95% CI, 2.38-2.50 and 5.82 95% CI, 5.73-5.92, respectively, in 2011-2015. Average annual percentage change in IBD incidence was 12.3% in 1986-1995, 12.3% in 1996-2005, and 3.3% in 2006-2015. The male-to-female ratio of the adjusted incidence rate was 3.3:1 for CD and 1.2:1 for UC. Perianal fistula/abscess was present in 43.3% of patients before or at CD diagnosis. At diagnosis, 54.3% of UC patients presented only with proctitis. The adjusted prevalence rate in 2015 was 31.59/100 000 95% CI, 31.10-32.07 for CD and 76.66/100 000 95% CI, 75.91-77.42 for UC.
The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Korean patients have distinct demographic and phenotypic characteristics, including a male predominance and high frequency of perianal fistula/abscess in CD and high proportion of proctitis in UC.
MiR-145 is downregulated in various cancers including prostate cancer. However, the underlying mechanisms of miR-145 downregulation are not fully understood. Here, we reported that miR-145 was ...silenced through DNA hypermethylation and p53 mutation status in laser capture microdissected (LCM) prostate cancer and matched adjacent normal tissues. In 22 of 27 (81%) prostate tissues, miR-145 was significantly downregulated in the cancer compared with the normal tissues. Further studies on miR-145 downregulation mechanism showed that miR-145 is methylated at the promoter region in both prostate cancer tissues and 50 different types of cancer cell lines. In seven cancer cell lines with miR-145 hypermethylation, 5-aza-2'-deoxycytidine treatment dramatically induced miR-145 expression. Interestingly, we also found a significant correlation between miR-145 expression and the status of p53 gene in both LCM prostate tissues and 47 cancer cell lines. In 29 cell lines with mutant p53, miR-145 levels were downregulated in 28 lines (97%), whereas in 18 cell lines with wild-type p53 (WT p53), miR-145 levels were downregulated in only 6 lines (33%, P < 0.001). Electrophoretic mobility shift assay showed that p53 binds to the p53 response element upstream of miR-145, but the binding was inhibited by hypermethylation. To further confirm that p53 binding to miR-145 could regulate miR-145 expression, we transfected WT p53 and MUT p53 into PC-3 cells and found that miR-145 is upregulated by WT p53 but not with MUTp53. The apoptotic cells are increased after WT p53 transfection. In summary, this is the first report documenting that downregulation of miR-145 is through DNA methylation and p53 mutation pathways in prostate cancer.
No population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based ...cohort.
This Korean population-based, Songpa-Kangdong IBD cohort included all patients (n=1013) newly diagnosed with UC during 1986-2015. Disease outcomes and their predictors were evaluated.
During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines and antitumour necrosis factor (anti-TNF) agents was 40.8%, 13.9% and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20 and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1% and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (HR 8.249, 95% CI 2.394 to 28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440 to 28.773) and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057 to 0.886) were independent predictors of colectomy. The standardised mortality ratio in patients with UC was 0.725 (95% CI 0.508 to 1.004).
Korean patients with UC may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.
The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD ...patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.
Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.
During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio aHR, 2.70; 95% confidence interval CI, 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).
The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.
A Case of Epiploic Appendagitis after COVID-19 Lee, Hun Joo; Kim, Jaeyeon; Suh, Seong O
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi,
03/2023, Letnik:
81, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Acute epiploic appendagitis is an uncommon cause of abdominal pain resulting from appendageal ischemia caused by torsion or thrombosis of the draining vein. It is frequently misdiagnosed as acute ...appendicitis or diverticulitis. The coronavirus disease 2019 (COVID-19) pandemic has changed how this rare disease is diagnosed. There was a report of a young men diagnosed with COVID-19 and epiploic appendagitis as a rare cause of abdominal pain. In addition, a 50-year-old men was diagnosed with epiploic appendagitis during the treatment of COVID-19. This paper reports the case of a 53-year-old men who presented with right lower quadrant abdominal pain after COVID-19 and was diagnosed with acute epiploic appendagitis by computed tomography image findings. The thrombotic condition of COVID-19 may contribute to acute appendagitis, but more studies are needed to confirm this hypothesis.
We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a wellestablished population-based ...cohort in the Songpa-Kangdong district of Seoul, Korea.
Clinical characteristics and prognosis were compared between two groups: EOUC, defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined as UC diagnosed in individuals aged 18 to 59 years.
We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure to medications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumulative risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension p=0.351, 11.9% vs 18.1% for hospitalization p=0.240, and 2.3% vs 1.8% for colectomy p=0.977) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predictor of proximal disease extension (hazard ratio HR, 6.216; 95% confidence interval CI, 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC.
In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitalization, and colectomy.
Abstract
Background and Aims
The long-term outcomes of paediatric-onset inflammatory bowel disease pIBD in non-Caucasian populations are unknown. We therefore evaluated and compared the clinical ...features and long-term outcomes of pIBD with those of adult-onset IBD aIBD using a population-based cohort in the Songpa-Kangdong district of Seoul, Korea.
Methods
Clinical characteristics and prognoses were compared between the two groups: pIBD defined as <18 years of age at diagnosis and aIBD 18–59 years of age at diagnosis.
Results
We identified 131 patients with pIBD (48 ulcerative colitis UC, 83 Crohn’s disease CD) and 1192 patients with aIBD 866 UC, 326 CD during 1986–2015. Extensive colitis at diagnosis was more prevalent in pUC than in aUC 45.8% vs 22.3%, p < 0.001, and the overall exposure to corticosteroids, thiopurines and anti-tumour necrosis factor agents was higher in pUC than in aUC p < 0.001. The cumulative risk of colectomy was higher in pUC than in aUC during a median follow-up of 125.0 and 112.1 months, respectively 8.9% vs 1.8% at 10 years after diagnosis, p = 0.030. Ileocolonic location and inflammatory behaviour at diagnosis were more common in pCD than in aCD; however, patients with pCD and aCD did not differ regarding treatment or disease course during a median follow-up of 137.2 and 120.9 months, respectively.
Conclusion
Our study showed clear differences between pIBD and aIBD, especially in UC. pUC presents with more extensive diseases and may have a more severe disease course, as suggested by an earlier time to administering medications and performing colectomy.
Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis ...of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.
Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.
Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio aHR, 2.70; 95% confidence interval CI, 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).
Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades. (Gut Liver 2022;16:216-227)
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