p62 Regulates the Proliferation of Molecular Apocrine Breast Cancer Cells.

p62, also called sequestosome 1 (SQSTM1), is a multifunctional signaling molecule that affects cell proliferation. Recently, we found accumulation of p62 in apocrine carcinoma of the breast, however, the biological role of p62 expression in apocrine carcinoma still remains unclear. To investigate whether p62 might contribute to tumor cell proliferation in apocrine carcinomas, we used the MDA-MB-453 (androgen receptor-positive, HER2-type) and MFM223 (androgen receptor-positive, triple-negative type) breast cancer cell lines as models of molecular apocrine carcinoma. Both MDA-MB-453 and MFM223 showed strong and d high p62 protein expression than MCF7 cells (androgen receptor-negative, luminal A type). Knockdown of p62 resulted in significant reduction of the cell proliferative activity in both MDA-MB-453 (P<0.01) and MFM223 (P<0.05). In conclusion, p62 could contribute to cell proliferation and represent a therapeutic target in apocrine carcinoma.

Clinical impact of gastroenterologist-administered propofol during esophagogastroduodenoscopy: a randomized comparison at a single medical clinic.

BACKGROUND: Although midazolam is widely used during endoscopic procedures by endoscopists, propofol has been recently favored for its rapid action and metabolism. The aim of this study is to compare the clinical advantages between propofol and midazolam use during screening esophagogastroduodenoscopy (EGD) for gastric cancer and post-procedure management at a medical clinic. METHODS: One hundred six healthy patients aged 20-69 years requesting sedation for screening EGD from October 2012 to May 2013 at a single clinic in Japan were randomly assigned to propofol (n = 54) or midazolam (n = 52). Medications were given by bolus injection, and the dose was adjusted by body weight. Sedation level and tolerability during EGD and recovery time were assessed. Sedation level and tolerability were evaluated by American Society of Anesthesiologists responsiveness levels and four levels of the gag reflex, respectively. For safety purposes, endoscopists and nurses were trained in administering propofol and an anesthesiologist was on call at all times. RESULTS: No statistically significant differences were found between the two groups in sedation level and patient tolerability. Full recovery time in the propofol group (4.7 min) was significantly shorter than that in the midazolam group (24 min, P < 0.01). CONCLUSIONS: Regarding post-procedure management of patients in a medical clinic, propofol use might not necessitate a recovery room and excessive assessment tasks because of rapid recovery time without any prolonged reaction, which causes patient compliance. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000009142.).

Use of color Doppler ultrasonography for evaluating vascularity of small intestinal lesions in Crohn's disease: correlation with endoscopic and surgical macroscopic findings.

OBJECTIVE. Ultrasonography (US) is a simple, inexpensive and minimally invasive method. We evaluated the vascularity of small intestinal lesions in Crohn's disease using color Doppler US (CD-US) and retrospectively compared them with endoscopic and surgical macroscopic findings. MATERIAL AND METHODS. In order to compare CD-US and endoscopic findings, 108 Crohn's disease patients who underwent examination of the terminal ileum by both colonoscopy and CD-US were included in the study. Vascularity was evaluated in CD-US using a semiquantitative method, the Limberg score. We analyzed correlations between Limberg score and simple endoscopic score for Crohn's disease (SES-CD), an index reflecting endoscopic activity. Scores of SES-CD 3 and higher were defined as endoscopically active. For comparison with surgical macroscopic findings, 22 Crohn's disease patients who received CD-US and subsequent iliectomies were included. Lesions with apparent open ulcers were defined as active, and those without as non-active. These findings were compared with the Limberg score. RESULTS. A substantial positive correlation was observed between Limberg scores and SES-CD (ρ = 0.709 [p < 0.001]). Notably, all 27 cases with a Limberg score of 3 or 4 were classified as endoscopically active. Compared to surgical macroscopic activity, Limberg scores of active lesions were significantly higher than those of non-active lesions (p = 0.005). In particular, all 11 cases with a Limberg score of 3 or 4 were classified as active lesions. CONCLUSION. Vascularity of small intestinal lesions of Crohn's disease evaluated by CD-US with Limberg score is well correlated with endoscopic and surgical macroscopic findings.

Efficacy of infliximab in patients with intestinal Behçet's disease refractory to conventional medication.

OBJECTIVE: To investigate the short- and long-term efficacy and safety of infliximab (IFX) in intestinal Behçet's disease (BD) patients in a retrospective cohort study. METHODS: Among 43 consecutive patients with intestinal BD presenting at the same clinic, 15 with active disease and receiving standard treatment were given IFX infusions (5 mg/kg body weight) every eight weeks. The patients were clinically and endoscopically evaluated before treatment, then assessed after 10 weeks, 12 months and 24 months for a clinical response, defined as a significant improvement in intestinal symptoms and a reduced C-reactive protein (CRP) level. RESULTS: At week 10, 12 patients (80%) exhibited a response to IFX, with eight (53%) in remission with no intestinal symptoms and normal CRP levels. A response to IFX was maintained in seven of the 11 patients (64%) available at 12 months and in four of the eight patients (50%) available at 24 months. Of the seven patients receiving prednisolone at entry, five responders had their steroid doses reduced. Fulminant intestinal BD was predictive of an absence of response to IFX. The adverse effects comprised one infusion reaction and one case of fever, most likely related to IFX. CONCLUSION: IFX is effective and safe in patients with refractory intestinal BD.

Conception and pregnancy outcome in women with inflammatory bowel disease: A multicentre study from Japan.

BACKGROUND: Neither conceptions and pregnancy outcomes nor the safety of medications for childbearing inflammatory bowel disease (IBD) patients has been investigated in Asia. The aim of this study is to analyse conception and pregnancy outcomes of Japanese female IBD patients. METHODS: We conducted a retrospective cohort study of pregnant IBD patients at 6 institutions. The incidences of abortion, Caesarean delivery, low birth weight (LBW) (<2500g), and congenital malformation were analysed in these patients. Risk factors associated with adverse outcomes in IBD patients were also assessed. RESULTS: A total of 325 patients experienced 534 conceptions. Among these, 303 conceptions (57%) were observed during/after disease onset. Although conceptions and pregnancy outcomes after disease onset were comparable to the observed levels prior to disease onset in UC patients, the incidences of spontaneous abortion (OR 5.3; 95%CI 1.1-25.0) and Caesarean delivery (OR 4.8; 95%CI 1.5-15.0) were significantly higher in Crohn's disease (CD) patients whose conceptions occurred after disease onset compared to CD patients whose conceptions occurred before disease onset. The incidences of spontaneous abortion, LBW, and Caesarean delivery were higher in CD patients who had a history of surgery for perianal lesions than in those who did not have perianal lesions or who had ulcerative colitis (UC). In the IBD patients studied after disease onset, independent risk factors for spontaneous abortions included a history of previous treatment for sterility (OR 2.9; 95%CI 1.2-7.0). Independent risk factors for Caesarean operation (OR 4.1, 95% CI: 1.7-10.1) and LBW (OR 3.5, 95% CI: 1.3-9.1) included a history of bowel resection for the treatment of IBD. Congenital malformation was not associated with the factors of type of disease, smoking, and previous surgery. CONCLUSION: In Japanese UC patients, conception and pregnancy outcomes after disease onset were comparable to the outcomes observed prior to disease onset, whereas CD appeared to be associated with adverse outcomes. Caesarean operation and LBW were more frequently observed in CD patients who had a history of surgery for perianal lesions and bowel resection.