RESUMEN
Objective: To investigate the effect and molecular mechanism of antimicrobial peptide LL-37 secreted by stromal cells on the growth of colorectal cancer cells. Methods: Colorectal cancer cells SW480 or HCT116 were co-cultured with human macrophages using Transwell(®) maxicell inserts to mimic the tumor microenvironment. The effect of macrophages on the proliferation of colorectal cancer cells was detected by Bromodeoxyuridine and enzyme-linked immunosorbent assay (BrdU-ELISA). The expression of LL-37 mRNA and protein in macrophages and colorectal cancer cells was evaluated by reverse transcription-real-time quantitative PCR (RT-qPCR) and Western blot. LL-37 neutralizing antibody was added to abrogate the LL-37 activation. Additionally, macrophages were transfected with LL-37 shRNA plasmids to inhibit LL-37 expression. And then, the proliferation of colorectal cancer cells was observed. Furthermore, the growth-related signaling pathways were detected by Western blot. Results: The BrdU-ELISA results showed that the absorbance of SW480 cells increased from 1.072±0.097 to 5.121±0.407 after co-culture (P<0.001), and that of HCT116 cells increased from 1.229±0.073 to 3.495±0.228 (P<0.001). RT-qPCR results showed that LL-37 mRNA expression in macrophages significantly increased from 2.682±0.191 to 6.117±0.768 after co-incubation (P<0.05), whereas that in SW480 had no significant difference. Consistently the protein expression of LL-37 in macrophages was significantly increased by Western blot, while it did not change in SW480. The proliferation rate of SW480 cells was repressed by adding LL-37 neutralizing antibody or LL-37 shRNA plasmid. Furthermore, Western blot analysis showed that the expression of non-phosphorylated (activated) ß-catenin and its target genes cyclin D1 as well as c-myc were distinctly increased in co-cultured SW480 cells, which could be reversed by anti-LL-37 antibodies. Conclusion: Macrophages promote the in vitro proliferation of colorectal cancer cells by enhancing the expression and secretion of antimicrobial peptides LL-37, and it seems that LL-37 activates colorectal cancer cells via Wnt/ß-catenin pathway.
Asunto(s)
Catelicidinas/metabolismo , Proliferación Celular , Neoplasias Colorrectales/patología , Macrófagos/metabolismo , Péptidos Catiónicos Antimicrobianos , Catelicidinas/genética , Línea Celular Tumoral , Células HCT116 , Humanos , ARN Mensajero/metabolismo , ARN Interferente Pequeño , Transducción de Señal , Transfección , beta Catenina/metabolismoRESUMEN
The aim of this study was to investigate the association between the cyclooxygenase 2 (COX2) -765G>C (rs20417) polymorphism and prostate cancer (PC) risk using meta-analysis. A systematic literature search was performed using the PubMed, Embase, Cochrane Library, and Google Scholar databases by using the terms "cyclooxygenase-2/COX-2/PTGs2", "polymorphism" or "variation", and "prostate" and "cancer" or "carcinoma" to identify relevant articles up to June 14, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for PC risk associated with COX2 -765G>C polymorphism using fixed- and random-effect models. We identified a total of nine publications, including 5952 cases and 5078 controls, to investigate the effect of COX2 -765G>C on PC risk, and found no significant association in any genetic model tested (CC vs GG: OR = 0.993, 95%CI = 0.923-1.068; GC+CC vs GG: OR = 1.041, 95%CI = 0.931-1.103; CC vs GC+GG: OR = 0.858, 95%CI = 0.689-1.067; CC vs GG: OR = 0.871, 95%CI = 0.689-1.086; GC vs GG: OR = 1.032, 95%CI = 0.945-1.127). Power analysis and tests for publication bias ensured the reliability of our results. This meta-analysis suggested that the functional COX2 -765G>C polymorphism, located in the COX2 gene promoter, is unlikely to be associated with PC risk. However, additional larger, well-designed studies are still required to reach a conclusive result on this issue.
Asunto(s)
Ciclooxigenasa 2/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Alelos , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Oportunidad Relativa , Sesgo de PublicaciónRESUMEN
We report a case of a 12-year-old boy with heterotopic pancreas (HP) located in a Meckel's diverticulum (MD) and presenting as obscure gastrointestinal (GI) bleeding. Upper GI endoscopy and colonoscopy did not reveal the source of the bleeding, however, capsule endoscopy revealed a space-occupying lesion in the ileum. The patient developed massive bleeding and an emergency exploratory laparotomy was performed. A congested MD was discovered 100 cm from the ileocaecal valve using intra-operative endoscopy; the ulcerated tip of the diverticulum appeared to be the source of the bleeding. The MD and adjacent ileal segment were resected and an end-to-end anastomosis performed. Subsequent pathological examination revealed an ileal MD with HP tissue within the submucosa. The patient remains well, 12 months after the operation, with no evidence of recurrent bleeding. This case suggests that HP should be considered as one possible cause of obscure GI bleeding in children and capsule endoscopy is a valuable adjuvant tool in the diagnosis of HP in children.
Asunto(s)
Coristoma/complicaciones , Coristoma/patología , Hemorragia Gastrointestinal/complicaciones , Divertículo Ileal/complicaciones , Divertículo Ileal/patología , Páncreas , Endoscopía Capsular , Niño , Coristoma/cirugía , Hemorragia Gastrointestinal/patología , Humanos , Masculino , Divertículo Ileal/cirugíaRESUMEN
Despite the development of crystal engineering, it remains a great challenge to predict the crystal structure even for the simplest molecules, and a clear link between molecular and crystal symmetry is missing in general. Here we demonstrate that the two-dimensional (2D) crystallization of heterocirculenes on a Au(111) surface is greatly affected by the molecular symmetry. By means of ultrahigh vacuum scanning tunneling microscopy, we observe a variety of 2D crystalline structures in the coverage range from submonolayer to monolayer for D(8h)-symmetric sulflower (C16S8), whereas D(4h)-symmetric selenosulflower (C16S4Se4) forms square and rectangular lattices at submonolayer and monolayer coverages, respectively. No long-range ordered structure is observed for C(1h)-symmetric selenosulflower (C16S5Se3) self-assembling at submonolayer coverage. Such different self-assembly behaviors for the heterocirculenes with reduced molecular symmetries derive from the tendency toward close packing and the molecular symmetry retention in 2D crystallization due to van der Waals interactions.