Shin Namiki

IRF-1 mediates upregulation of LMP7 by IFN-γ and concerted expression of immunosubunits of the proteasome

An immunoproteasome subunit low molecular weight protein 7 (LMP7) plays critical roles in major histocompatibility complex class I antigen processing; however, the mechanism for its expression has remained unclear. We demonstrate that interferon (IFN) regulatory factor‐1 (IRF‐1) has a pivotal role in IFN‐γ‐dependent LMP7 expression, as was shown for the other two immunosubunits. A tetracycline‐inducible system for IRF‐1 revealed its function in the LMP7 expression, and a genomic region functionally interacting with IRF‐1 was also determined. Furthermore, the role of IRF‐1 in IFN‐γ‐inducible LMP7 transcription was confirmed by employing small interfering RNA experiments and IRF‐1−/− mice. These results suggest that IRF‐1 acts as a master regulator for the concerted expression of immunoproteasome components.

Absence of high-risk stigmata predicts good prognosis even in severely anemic patients with suspected acute upper gastrointestinal bleeding

Background The need for a blood transfusion, defined as hemoglobin < 70 g/L, is the measure for assessing the risk levels in patients with upper gastrointestinal bleeding (UGIB). However, not all patients with a low hemoglobin level have a poor prognosis. Objective We assessed the clinical predictive factors associated with poor short-term prognosis in patients with a low hemoglobin level. Methods In this prospective cohort study, all consecutive patients with suspected acute UGIB at Tokyo Metropolitan Tama Medical Center were enrolled between 2008 and 2015. Then, we extracted those who needed a blood transfusion (hemoglobin < 70 g/L) and explored the variables associated with all-cause mortality within 28 days after presentation. Results Among 1307 patients, 311 needed a blood transfusion and 13 (4.2%) died from all causes. The presence of high-risk stigmata requiring endoscopic treatment (peptic ulcers; Forrest scores Ia, Ib and IIa; varices with current bleeding or signs of recent bleeding; and spurting or gushing bleeding or visible vessel in other diseases), diagnosed by emergency endoscopy, was a unique factor affecting mortality (odds ratio: 8.47, 95% confidence interval: 1.45–160, P = 0.01). Patients without high-risk stigmata neither died from UGIB nor had rebleeding, irrespective of the hemoglobin levels. Conclusions Patients without high-risk stigmata showed a good prognosis even if they needed a blood transfusion. This result could facilitate triage of patients with suspected acute UGIB who only need a blood transfusion.

Elevation of Neutrophil-to-Lymphocyte Ratio before First-Line Chemotherapy Predicts a Poor Prognosis for Second-Line Chemotherapy in Gastric Cancer

Objectives: The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an indicator of cancer-related inflammation. The aim of our study was to examine the prognostic value of the NLR for patients with advanced gastric cancer receiving second-line chemotherapy. Methods: The association of overall survival (OS) in second-line chemotherapy and the clinicopathological findings including NLR were analyzed retrospectively. The selection criteria were patients who received second-line chemotherapy between January 2010 and June 2015, had histologically confirmed gastric adenocarcinoma, and were followed up until death or for 180 days or longer. Results: Eighty-six patients met the selection criteria. Multivariate analysis revealed that performance status 2, hemoglobin < 10 g/dL, and NLR before first-line chemotherapy ≥3 were adverse predictive markers. NLR before second-line chemotherapy was not associated with OS. A prognostic model was constructed dividing patients into three groups according to the number of adverse predictive factors: good (no factor), intermediate (one factor), and poor (more than two factors). The median OS for the good, intermediate, and poor groups was 14.3, 7.2, and 4.4 months, respectively (p < 0.001). Conclusions: Patients with advanced gastric cancer with performance status 2, hemoglobin < 10 g/dL, and NLR before first-line chemotherapy ≥3 are not likely to benefit from second-line chemotherapy.