ARF6 and AMAP1 are major targets of and mutations to promote invasion, PD-L1 dynamics, and immune evasion of pancreatic cancer.

Although and mutations are major drivers of pancreatic ductal adenocarcinoma (PDAC), the incurable nature of this cancer still remains largely elusive. ARF6 and its effector AMAP1 are often overexpressed in different cancers and regulate the intracellular dynamics of integrins and E-cadherin, thus promoting tumor invasion and metastasis when ARF6 is activated. Here we show that the ARF6-AMAP1 pathway is a major target by which and cooperatively promote malignancy.

Does the weakening of intrinsic foot muscles cause the decrease of medial longitudinal arch height?

[Purpose] There are no reliable evidences that the weakening of intrinsic foot muscles causes the decrease of the medial longitudinal arch (MLA) height. The purpose of this study was to confirm whether the fatigue of intrinsic foot muscles decrease the MLA height during standing and gait using 3D motion analysis system. [Subjects and Methods] Twenty healthy male subjects participated in this study.

Development of Enzyme Loaded Polyion Complex Vesicle (PICsome): Thermal Stability of Enzyme in PICsome Compartment and Effect of Coencapsulation of Dextran on Enzyme Activity.

Applications of enzymes are intensively studied, particularly for biomedical applications. However, encapsulation or immobilization of enzymes without deactivation and long-term use of enzymes are still at issue. This study focuses on the polymeric vesicles "PICsomes" for encapsulation of enzymes to develop a hecto-nanometer-scaled enzyme-loaded reactor.

Evaluation of in vivo release characteristics of protein-loaded biodegradable microspheres in rats and severe combined immunodeficiency disease mice.

The in vivo release characteristics of protein-loaded biodegradable microspheres were examined in normal rats and severe combined immunodeficiency disease (SCID) mice. Bovine-derived superoxide dismutase (bSOD), encapsulated into microspheres comprised of poly(D,L-lactic-co-glycolic acid) and poly(D,L-lactic acid), was used as a model protein. Three types of bSOD-loaded microspheres with different release profiles were subcutaneously administered to normal rats.

Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats.

T-0128 is a novel camptothecin (CPT) analogue (T-2513: 7-ethyl-10-aminopropyloxy-CPT)-carboxymethyl (CM) dextran conjugate via a Gly-Gly-Gly linker, with a molecular weight (MW) of 130 kDa. Our previous studies demonstrated that T-0128 has strong antitumor activity against human tumor xenografts that are highly refractory to CPT analogues attributable to the passive tumor targeting of released T-2513. This study examines the effects of carrier, dose, and tumor on T-0128 pharmacokinetics.

Protein encapsulation into biodegradable microspheres by a novel S/O/W emulsion method using poly(ethylene glycol) as a protein micronization adjuvant.

A new method for preparing protein-loaded biodegradable microspheres by a process involving solid-in-oil-in-water (S/O/W) emulsion was established using poly(ethylene glycol) (PEG). In the first step, a protein solution was lyophilized with PEG, which resulted in the formation of spherical protein microparticles, less than 5 microm in diameter, dispersed in a continuous PEG phase. This process was well explained by the aqueous phase separation phenomenon induced by freezing-condensation.

Complete regression of xenografted human carcinomas by camptothecin analogue-carboxymethyl dextran conjugate (T-0128).

Clinically available camptothecins (CPTs), such as irinotecan (CPT-11) and topotecan, represent one of the most promising classes of antitumor agents, despite their toxicity. To improve their pharmacological profiles, a new macromolecular prodrug, denoted T-0128, was synthesized. This prodrug is a novel CPT analogue (T-2513)-carboxymethyl (CM) dextran conjugate via a triglycine spacer, with a molecular weight of Mr 130,000.

Insight and clinical correlates in schizophrenia.

It is not clear to what extent poor insight is inherent in schizophrenic psychopathology or is related to clinical factors. It is clinically important to elucidate this point to know how some insight remains intact in schizophrenia. Sixty-three ICD-10 schizophrenics were recruited.

Subjective experience and related symptoms in schizophrenia.

We had previously extracted two types of subjective experience of schizophrenia (SES); first, a feeling of inadequacy in stream of speech, thought, and action, associated with a distorted sense of self, and second, a feeling that excessive thoughts are filling and sticking to one's head, causing negative affective burden such as misery and oppression. This study tried to validate their content using conventional symptom clusters as external validators. Subjects were 63 patients from two hospitals in Tokyo meeting ICD-10 criteria for schizophrenia.

Extramedullary plasmacytoma producing biclonal gammopathy.

A case of extramedullary plasmacytoma presenting with biclonal gammopathy is reported. The patient was an 82-year-old man in whom monoclonal-protein (M-protein) was not noted during his first hospitalization. On his second hospitalization generalized lymph node swelling and biclonal gammopathy (IgG-kappa, IgA-kappa) were observed.

Disposition characteristics of macromolecules in the perfused tissue-isolated tumor preparation.

Disposition characteristics of model macromolecules with different physicochemical characteristics and macromolecular prodrugs of mitomycin C, namely mitomycin C-dextran conjugates, were studied in tissue-isolated tumor preparations of Walker 256 carcinoma with the use of a single-pass vascular perfusion technique. In constant infusion experiments, all radiolabeled macromolecules accumulated in the tumor tissue, but the degree and pattern of distribution greatly varied, depending on their electric charges. Positively charged macromolecules were markedly accumulated compared with those that were neutral or negatively charged.

The expert system for toxicity prediction of chemicals based on structure-activity relationship.

The prediction systems of chemical toxicity has been developed by means of structure-activity relationship based on the computerized fact database (BL-DB). Numbers and ratio of elements, side chains, bonding, position, and microenvironment of side chains were used as structural factors of the chemical for the prediction. Such information was obtained from the BL-DB database by Wiswesser line-formula chemical notation.

Clinical and histologic study of endoscopic duodenitis.

Duodenitis was investigated by endoscopy in 93 cases from among 1242 subjects. Endoscopic duodenitis was classified into three types endoscopically--reddening type, erosive type and nodular type. There was a relatively high correlation between the endoscopic and the histological diagnosis of duodenitis.