BackgroundDespite recent advances the pathogenesis of Crohn's disease remains incompletely understood. A variety of animal models have been utilized in an effort to provide further insights and develop more therapeutic options. In order to simulate, to an extent, the pathogenesis and the clinical course of the disease, TNBS induced colitis is often used. Various approaches for inducing TNBS -colitis have been described in the literature.Methods/resultsIn this review, we sought to present the animal model of TNBS induced colitis and outline the pathogenesis, pathophysiology, clinical course and pathological characteristics of the model. Furthermore, we describe the differences among those protocols regarding types of animals and colitis induction.Data sourcesThe MEDLINE database was thoroughly searched using the keywords: TNBS, colitis, Crohn's disease, animal model. Two investigators independently reviewed the abstracts and appropriate articles were included in this review. Additional articles were gathered and evaluated.ConclusionThe aim of this study was to thoroughly present an updated review of the TNBS-induced colitis protocols that are implemented by researchers.
The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Student's t-test. HT29 human xenografts were treated with anti-PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log-rank test and Cox model. All statistical tests were two-sided. PC1 overexpression promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence-free survival (HR 5 1.016, p 5 0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p 5 0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression.Invasion and metastasis are responsible for 90% of cancerassociated mortality. While the role of biochemical signals in invasion and metastasis is well established, growing evidence reveals that mechanical signals also regulate cancer-cell
For the subgroup of extremely high-risk and unfit for surgery patients, percutaneous cholecystostomy might be considered as the definitive treatment since it controls the local symptoms and the systemic inflammatory response.
Background: Oxaliplatin has become one of the major cytotoxic agents for the treatment of gastrointestinal tumors. As a result, several cases of the so-called oxaliplatin-associated hypersensitivity reaction have been documented. Patients and Methods: We have retrospectively evaluated and characterized these reactions in our patient group by reviewing the files of 1,224 patients exposed to an oxaliplatin-containing regimen in order to provide useful clinical information for diagnosis and management. Results: Three hundred and eight (308) patients who have never been exposed to platinum compounds developed symptoms compatible with a reaction to oxaliplatin that was verified by manifestation of at least similar symptoms on rechallenging. The reactions occurred after the first 5 courses, with a median course number of 9 (range 1–24). These reactions could be distinguished as (1) mild reactions occurring in 195 (63%) patients manifesting with itching and small area erythema either during treatment or within the next hours, and (2) severe reactions occurring in 113 (37%) patients within minutes of drug infusion manifesting with diffuse erythroderma, facial swelling, chest tightness, bronchospasm and changes in blood pressure. Oxaliplatin withdrawal was not required in patients with a mild reaction. Forty-eight (42%) patients having a severe reaction with appropriate premedication and prolongation of the infusion duration could tolerate 2–4 subsequent courses. For the remaining 65 (58%) patients, oxaliplatin withdrawal was inevitable because of the very severe reactions occurring on rechallenging. In addition, 3 patients presented with thrombocytopenia and 3 others with hemolytic anemia, all reversible upon oxaliplatin discontinuation. Conclusions: Hypersensitivity reactions to oxaliplatin are underestimated. Although the reactions are not frequent during first courses, in extensively pretreated patients, they may become a serious problem. In the majority of patients, drug discontinuation might not be necessary. In patients manifesting a severe reaction, re-exposure to oxaliplatin should be considered only if the patient can tolerate the reaction and there has been clinical benefit from this therapy. Physicians and nursing staff should be aware of the risk and be well prepared.
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