Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.

Given the relationship between the presence of ApoE epsilon 4 and Alzheimer's disease (AD), were studied whether knowledge of epsilon 4 status would predict which memory-impaired patients would develop AD over time. One hundred seven patients who presented with memory impairment but not dementia were referred to the study by their family physicians. These patients were followed prospectively over a 2-year period. Twenty-nine patients developed AD, while 78 did not develop dementia. We found that ApoE genotype was a reliable prognostic indicator of who developed AD in this group only when memory test performance was included in the predictive model. These findings indicate that limitations of ApoE genotyping in isolation as a prognostic indicator of AD. Because this study included prospectively selected patients who were followed longitudinally, our findings are likely to have more relevance in the clinical setting than those obtained from currently available retrospective studies.

No abstract

Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.

Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK-RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK-RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at -15.0% (Arm D1 - Arm D3). Results A total of 396 patients-196 and 200 patients in Arms D3 and D1, respectively-were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, -12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, -8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, -14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK-RA and Palo in HEC.

Since dendritic cells (DCs) play a critical role in establishing antigen-specific adaptive immune responses, in the past several years, therapeutic strategies using genetically modified DCs against cancer and infectious diseases have attracted increasing attention. In the present study, we demonstrated that RGD fiber-mutant adenovirus vector (AdRGD) exhibited markedly superior gene transduction efficiency in mouse bone marrow-derived DCs (mBM-DCs) compared to conventional adenovirus vector (Ad). Likewise, this vector exhibited superior major histocompatibility complex class I-restricted presentation of antigen derived from the delivered gene in mBM-DCs. In order to investigate the effect of Ad-infection on the DC-differentiation process (maturation), we used three types of AdRGD and three conventional Ad to transduce mBM-DCs. These vectors carried either no transgene, LacZ gene, or gp100 gene. Infection by any of the Ad vectors enhanced the expression of MHC class II molecules in mBM-DCs. CD80, CD86, and CD40 expression and IL-12 production were more efficient in AdRGD-infected mBM-DCs than in conventional Adinfected cells. Contrary to our expectations, endocytotic activity of mBM-DCs decreased only slightly upon Ad-infection, whereas antigen uptake by lipopolysaccharide (LPS)-driven mature mBM-DCs was significantly impaired. However, our reverse transcription-polymerase chain reaction analysis revealed that Ad-infection resulted in the upregulation of the chemokine receptor CCR7 and downregulation of CCR6 in mBM-DCs and LPS-stimulated cells. We, therefore, concluded that Ad-infection directly influenced DC-maturation, although the effects were milder than under LPS-stimulation. In addition, this change in the immunologic properties of DCs resulted primarily from an increase in the number of Ad-particles capable of invading the cells rather than from the expression of foreign genes. AdRGD-infection caused greater induction of maturation than conventional Adinfection, irrespective of the type of transgene inserted.

No abstract

Abstract-Pre␤1-high density lipoprotein (pre␤1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL 2 by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase pre␤1-HDL at the expense of HDL 2 . To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglyceridesϾ2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, pre␤1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5Ϯ49.