Rapid on-site evaluation (ROSE) in pancreatic cancer diagnosis. doing more with less

Rapid on-site evaluation (ROSE) in pancreatic cancer diagnosis: Doing more with les

A case of oesophageal ulcer developed after taking homeopathic pill in a young woman

Oesophageal ulcers occur mainly as a result of gastrooesophageal reflux disease (GERD). However, pill-induced oesophageal ulcers are a fairly common event. The lesion is mainly due to entrapment of the pill and/ or its chemical composition thereof This case report describes an oesophageal mucosa ulcer occurred in a healthy 35-year old woman who had no previous history of oesophageal disorders and received homeopathic medication. The present case reveals that pill entrapment can occur even in the oesophagus of healthy young individuals and that oesophageal mucosal ulcer can be triggered by substances generally thought devoid of any potentially mucosal aggressive effect. (c) 2007 The WJG Press. All rights reserved

Novel Non-Peptide Small Molecules Preventing IKKβ/NEMO Association Inhibit NF-κB Activation in LPS-Stimulated J774 Macrophages

Nuclear Factor-κB (NF-κB) is a transcription factor regulating several genes involved in important physiological and pathological processes. NF-κB has been found constitutively activated in many inflammatory/immune diseases. In addition, a positive correlation between persistent activation of NF-κB and tumor promotion has been demonstrated. Since the IKK (IκB kinase) activation is an indispensable component of all pro-inflammatory signaling pathways leading to NF-κB activation, considerable efforts have been done in order to develop novel anti-inflammatory therapeutics targeting IKK. Association of the IKK complex relies on critical interactions between the C-terminus NBD (NEMO binding domain) of the catalytic subunits IKKα and IKKβ, and the regulatory subunit NEMO (NF-κB Essential Modulator). Thus, this IKK/NEMO interacting region provides an attractive target to prevent the IKK complex formation and NF-κB activation. In this regard, we have identified non-peptide small molecule disruptors of IKKβ/NEMO complex through a structure-based virtual screening (SBVS) of the NCI chemical library. Phenothiazine 22 and its close analogues (22.2, 22.4 and 22.10) were able to reduce nitrite production and iNOS mRNA expression in J774 murine macrophages stimulated with LPS for 24 h. These effects were associated with a reduced NF-κB/DNA binding activity as well as a decreased expression of phosphorilated IKKβ, IκBα and NF-κB/p65 in these cells. These observations suggest that compound 22 and its three structural analogues by inhibiting IKKβ/NEMO association mediate the blockage of NF-κB signaling pathway and may prove effective in treatment of diseases in which the IKK/NF-κB pathway is dysregulated

Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa

Background and Aim: Gut flora/host interactions are fundamental for the maintenance of homeostasis. Evidence of possible regulatory effect of commensal bacteria on proliferative disorders of the colon is mounting. In this study, we explored the hypothesis that precancerous lesions, such as adenomas, present alteration of the local microflora and lead to an overproduction of antibacterial molecules of the innate immunity, namely alpha-defensins. Thus, the host-bacteria misbalance could represent a potential procarcinogenic factor. Methods: Biopsies from adenomatous polyps and normal mucosa, in the rectum-sigmoid colon, were collected from 51 patients. Concentration of mucosal bacteria was evaluated by real-time polymerase chain reaction after extraction of total DNA. Total RNA was also extracted, and the defensin alpha-1, defensin-5, and defensin-6 gene expressions were evaluated by real-time polymerase chain reaction. Immunohistochemical study has been carried out to evaluate protein production and location. Antibacterial activity of adenomatous polyps mucosa was evaluated in vitro. Results: Biopsies from adenomatous polyps had a significant relative reduction of mucosa adherent bacteria compared with normal tissue (20-fold relative reduction, P < 0.05). Concomitantly, alpha-defensin expression and production were significantly increased in adenomas. Adenoma mucosa showed increased antibacterial activity in vitro compared with normal mucosa. Conclusions: Microflora dysbiosis occurs at the mucosal surface in colonic adenomas, and may represent a potential factor for dysplastic cell proliferation. Further studies are needed to confirm and define the role of this mechanism in colon carcinogenesis and the potential applications in the clinical setting

Pleural tuberculosis diagnosed by EUS-guided fine-needle tissue acquisition

EUS-FNA has become an important tool for the evaluation of the mediastinum. [1] and [2] The main role of EUS-FNA in the thorax has been in the diagnosis and staging of lung cancer and in tissue acquisition in patients with mediastinal masses or lymphadenopathy of unknown origin. [3], [4] and [5] Moreover, detection and sampling of small pleural effusions have been described, [6], [7], [8] and [9] whereas no report on EUS-guided pleura biopsy exists. We present a patient with suspected tuberculosis (TB) in whom the definitive diagnosis was obtained by EUS-guided fine needle tissue acquisition (EUS-FNTA) of a thickened pleura

Pancreatic metastases from a bronchopulmonary carcinoid diagnosed by endoscopic ultrasonography-guided fine-needle tissue acquisition

Nearly 25% of well-differentiated neuroendocrine tumors\u2014carcinoids\u2014arise within the bronchopulmonary (BP) system where they represent about 2% of all primary lung tumors.1,2 According to their histological phenotype, BP carcinoids (BPCs) are currently classified as typical and atypical, based on focal necrosis and/or mitotic count per 10 high-power field.3 Atypical BPCs are characterized by high incidence of regional lymph node metastasis,4 whereas distant metastases occur less frequently, the most common sites being liver, bone, and adrenals.5 We present a patient with an atypical BPC who developed pancreatic metastases diagnosed by endoscopic ultrasonography\u2013guided fine-needle tissue acquisition (EUS-FNTA)