Higher detectability of gastric cancer after Helicobacter pylori eradication in texture and color enhancement imaging mode 2 in screening endoscopy.

Objectives: The utility of texture and color enhancement imaging (TXI) in detecting gastric cancer (GC) has been investigated. However, few reports exist on TXI mode2 (TXI2) used for detecting GC; this study investigated the efficacy of TXI2 in GC detection during screening endoscopy. Methods: This study enrolled 13,440 participants with confirmed Helicobacter pylori (H. pylori) infection status who underwent screening endoscopy by 20 endoscopists in our health screening center. The participants were divided into two groups: one group was observed using white light imaging (WLI) only by 17 endoscopists (WLI group, 10,745 participants), and the other group was observed using TXI2 only by the other three endoscopists (TXI2 group, 2695 participants). We analyzed the detection rate and the characteristics of GC. In addition, considering the bias due to the diagnostic ability, we analyzed the subset of the WLI group where the participants were evaluated by the top three endoscopists based on their GC detection rate (Expert-WLI group, 2792 participants) for comparison with the TXI2 group. Results: Fifty patients were diagnosed with GC. The GC detection rates were 0.68% and 0.71% in the Expert-WLI and TXI2 groups, respectively. In patients who underwent screening endoscopy after H. pylori eradication, the detection rates of differentiated GC, L-region lesions, and surface depressed-type lesions were 0.52%, 0%, and 0.43% in the Expert-WLI group and 1.36%, 0.78%, and 1.36% in the TXI2 group, respectively. Conclusions: In screening endoscopy, the detectability of differentiated GC and L-region lesions and surface depressed-type lesions after H. pylori eradication was higher in TXI2.

[Malignant lymphoma diagnosed by gallbladder wall thickness in an autoimmune hepatitis patient].

A 77-year-old female patient was undergoing steroid treatment for cirrhosis with autoimmune hepatitis. Periodic imaging acquisitions revealed both irregular gallbladder wall thickness and an isovascular tumor in segment one of the liver. After cholecystectomy and segmental hepatectomy, the pathological diagnosis was diffuse large B-cell lymphoma in both organs. Accordingly, she received chemotherapy but the disease rapidly spread;she died five months after surgery. Malignant lymphoma of the gallbladder is an uncommon disease;we consider that autoimmunity factors were associated with this pathogenesis.

The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo.

Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes.

Inhibition of Akt (ser473) phosphorylation and rapamycin-resistant cell growth by knockdown of mammalian target of rapamycin with small interfering RNA in vascular endothelial growth factor receptor-1-targeting vector.

Previously we developed dicetyl phosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL) for use in small interfering RNA (siRNA) therapy. In the present study, mammalian target of rapamycin (mTOR) expression in cancer cells was silenced with mTOR-siRNA (simTOR) formulated in TEPA-PCL modified with Ala-Pro-Arg-Pro-Gly (APRPG), a peptide having affinity for vascular endothelial growth factor receptor-1 (VEGFR-1). We investigated the effects of inhibition of mTOR, focusing on the differences between cells treated with simTOR and those with rapamycin in terms of Akt (ser473) phosphorylation and antiproliferative effects. Rapamycin treatment is known to induce Akt (ser473) phosphorylation which attenuates the antiproliferative effects of rapamycin. As a result, knockdown of mTOR did not alter or only slightly reduced Akt (ser473) phosphorylation in phosphatase and tensin homolog deleted from chromosome 10 (PTEN)-null (LNCaP and MDA-MB-468 cells) and PTEN-positive (DU 145 and MDA-MB-231) cells, although rapamycin induced Akt (ser473) phosphorylation of these cells. Rapamycin suppressed the growth of PTEN-null cells, in which the rapamycin-sensitive mTOR complex 1 (mTORC1) is excessively activated. On the other hand, rapamycin did not suppress the growth of PTEN-positive cells possibly through a negative feedback mechanism via the rapamycin-insensitive mTOR complex 2 (mTORC2) signaling pathway. In contrast, simTOR significantly suppressed the growth of cancer cells regardless of the presence of PTEN, possibly through inhibition of both mTORC1 and mTORC2. These results indicate that mTOR knockdown using APRPG-TEPA-PCL/simTOR is likely to be an effective strategy for cancer siRNA therapy.

A new method of estimating the cytotoxic effects of suspended particulate matter on cultured alveolar macrophages in vitro.

A new method has been devised for evaluating the cytotoxicity of suspended particulate matters in vitro. It uses the proliferative capacity of mouse alveolar macrophages, estimated by the uptake of (3)H-tymidine, as an index of cytotoxicity, and provides a simple and rapid means of evaluating the cytotoxicity of suspended particulate matter collected on a filter by a personal air sampler. A significant decrease in (3)H-thymidine uptake (an indication of impaired proliferation) could be detected in the range of approximately 0.31 to 1.03 mug of nickel sulfide particles per square centimeter of culture dish, suggesting the relatively great sensitivity of this method to particulate toxicants. A preliminary application of this method to suspended particulate matter collected in an urban atmosphere indicated that 3 hours of sampling, corresponding to that in about 0.72 cubic meters of air, were sufficient for evaluation of toxicity by this method.