Effective management of an advanced gastric cancer patient by TS-1 combined chemotherapy using nasojejunal tube and successful transfer to home care after percutaneous transesophageal gastro-tubing (PTEG): a case report.

A 67-year-old woman with debilitation and massive ascites was admitted to our hospital and diagnosed with stage IV scirrhous gastric cancer with peritoneal dissemination. After successful nasojejunal tube feeding because of oral intake disability, TS-1 combined with paclitaxel chemotherapy was selected. TS-1 at 80mg/m2 was given daily via nasojejunal tube for 2 weeks, followed by a 1-week rest, and paclitaxel at 50mg/m2 was administered intravenously on day 1 and 8. There were no serious side effects. After 4 cycles, a partial response was observed and percutaneous transesophageal gastrotubing (PTEG) was placed. After the fifth cycle, she was transferred to her home and received chemotherapy in an outpatient clinic. After 7 cycles, the disease progressed, and TS-1 combined with low-dose cisplatin was administered for 3 cycles. However, the patient died 16 weeks after discharge. PTEG was useful not only for a route of TS-1 administration, but also for receiving chemotherapy at home to maintain her quality.

Piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine as orally-active adhesion molecule inhibitors.

Novel piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine were prepared and evaluated for their inhibitory activity on the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Replacement of the methanesulfonyl group on the piperidine ring of previously prepared derivatives with a carboxylic acid-containing moiety resulted in a number of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1]non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect on collagen-induced arthritis in rats.

Studies on experimental iodine allergy: 1. Antigen recognition of guinea pig anti-iodine antibody.

It has generally been thought that iodine allergy is cross-sensitive to various iodine-containing chemicals. However, this concept seems to deviate from the immunological principle that immune recognition is specific. To solve this contradiction, we hypothesize that iodine allergy is an immunological reaction to iodinated autologous proteins produced in vivo by iodination reaction from various iodine-containing chemicals. Antisera to iodine were obtained from guinea pigs immunized subcutaneously with iodine-potassium iodide solution emulsified in complete Freund's adjuvant (CFA). The specificity of guinea pig anti-iodine antiserum was determined by enzyme-linked immunosorbent assay (ELISA) inhibition experiments using microplates coated with iodinated guinea pig serum albumin (I-GSA). Antibody activities were inhibited by I-GSA, diiodo-L-tyrosine, and thyroxine, but not by potassium iodide, monoiodo-L-tyrosine, 3,5,3'-triiodothyronine, monoiodo-L-histidine, or diiodo-L-histidine, or by ionic or non-ionic iodinated contrast media. The results that antigen recognition of anti-iodine antibody is specific to iodinated protein support our hypothesis. While protein iodination usually takes place both at histidine residues as well as at tyrosine residues, only iodinated tyrosine acted as an antigenic determinant and no antibody activities to iodinated histidine were detected in our experimental iodine allergy model.

Studies on experimental iodine allergy: 2. Iodinated protein antigens and their generation from inorganic and organic iodine-containing chemicals.

We hypothesize that iodine allergy is an immune response to iodinated autologous proteins generated in vivo from iodine-containing organic and inorganic chemicals. In this report, effects of protein iodination on elicitogenic activity in guinea pig iodine allergy model and iodinated protein antigen generation in vitro from iodine-containing chemicals were investigated. Active cutaneous anaphylaxis (ACA) and delayed-type hypersensitivity (DTH) tests were performed in guinea pigs immunized with iodine. The amount of iodine (I2) reacted to proteins for giving them an eliciting activity of ACA was > or = 0.15 micromol for 1 mg of albumin. DTH reactions were provoked by intradermal injection of 10(6) PECs reacted with > or = 0.075 micromol of I2. I2 was generated from a potassium iodide (KI) solution or iodinated contrast media by UV light irradiation. X-ray irradiation of KI and iodinated contrast media in the presence of protein resulted in the generation of iodinated protein antigens. The generation of iodinated protein antigens was inhibited in the presence of reducing agents. Therefore, it is noteworthy that iodine allergy of the present hypothesis is dependent on reactive oxygens. By presenting these ex vivo and in vitro data, we discuss the possibilities for the generation of iodinated protein antigens in vivo.

Studies on experimental iodine allergy: 3. Low molecular weight elicitogenic antigens of iodine allergy.

We hypothesize that iodine allergy is an immune response to iodinated self proteins produced in vivo from various iodine-containing chemicals. Since an antigenic determinant of experimental iodine allergy is diiodotyrosine (DIT), we designed low molecular weight DIT derivatives having provocative antigenicity without sensitizing immunogenicity. Tetraiododityrosine and hexaiodotrityrosine provoked dose-dependent skin reactions in guinea pigs previously immunized with iodine. No guinea pigs immunized with hexaiodotrityrosine showed anaphylactic reaction by i.v. challenge with hexaiodotrityrosine and none of their antisera showed positive passive cutaneous anaphylaxis (PCA) reaction in guinea pigs, indicating the non-immunogenic nature of the compound. Erythrosine, one of the color additives having a structure common with DIT, was assessed for its immunological property. Enzyme-linked immunosorbent assay (ELISA) inhibition studies on erythrosine revealed that the inhibitory activity of erythrosine was stronger than that of DIT. Furthermore, erythrosine provoked a PCA reaction in animals sensitized with anti-iodine antisera. In conclusion, hexaiodotrityrosine is thought to be useful for skin testing of iodine allergy without any fear of sensitization to the allergen. Erythrosine was shown to provoke an experimental iodine allergy and, also, the relationships between the new concept of iodine allergy and features of clinical findings of adverse effects by iodocontrast media are discussed.

Inhibitors of adhesion molecules expression; the synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives.

During a search for novel, orally-active inhibitors of upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), we found a new series of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives to be potent ICAM-1 inhibitors. Of these compounds, N-[1-(10H-Pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)piperidin-4-yl]-N',N'-dimethylsulfamide 7p showed the potent oral inhibitory activities against neutrophil migration in a murine interleukin-1 (IL-1) induced paw inflammation model. The synthesis and structure-activity relationships of these amide derivatives are described.