Interferon alpha-2a shows antitumor activity in combination with 5-fluorouracil against human colon carcinoma xenografts: A study in reference to thymidylate synthetase activity inhibition

To clarify the mode of antitumor activity shown by a combination of recombinant human interferon alpha-2a (IFN) and 5-fluorouracil (5-FU), experimental therapy was performed on human colon carcinoma (Co-4) xenografts serially transplanted into nude mice, using IFN and 5-FU, either alone or in combination. IFN alone showed dose-dependent antitumor activity and 5-FU also revealed a moderate antitumor effect. Although IFN, given as 600,000 units/mouse daily sc×14, and 5-FU, given as 60 mg/kg q4d×3 ip, showed additive antitumor activity against Co-4, the thymidylate synthetase (TS) inhibition rate was unchanged in the tumors treated with the IFN/5-FU combination in comparison with those treated with 5-FU alone. This suggests that the antitumor activity of IFN and 5-FU in combination does not involve augmentation of the TS inhibition by 5-FU.     

A nager acrofacial dysostosis syndrome patient with severe respiratory distress syndrome (RDS)

Summary Nager acrofacial dysostosis is characterized by radial defect and the facial manifestations like Treacher-Collins syndrome. There are few reports about this syndrome in Japan. We report a typical Japanese Nager syndrome patient. He was complicated with respiratory distress syndrome.     

Methylcellulose--a better viscosurgical alternative for intraocular lens implantation

The authors have used 2% methylcellulose in 8,000 cases of intraocular lens implant surgery during the last five and a half years. Their surgical experience and investigations have convinced them that methylcellulose is safe and effective besides being convenient and economical. It is easily autoclavable, has very low particulate matter when prepared by the author's technique, and causes minimal secondary rise of intraocular pressure. The endothelial protective function and breakdown of the blood aqueous barrier are comparable to that of Healon. The authors consider methylcellulose to be the better alternative for IOL implant surgery.     

"A" subunit of factor XIII is present on bovine platelet membrane and mediates collagen-induced platelet activation

The Fab fragment of a polyclonal antibody against platelet factor XIII inhibited the collagen-induced platelet aggregation in a dose-dependent manner. This inhibitory effect was specific for collagen, and it had no effect on arachidonic acid-, ADP-, and serotonin-induced aggregations. This finding strengthens our notion that platelet factor XIII is involved in collagen-induced platelet aggregation. (Saito, Y., Imada, T., Takagi, J., Kikuchi, T. and Inada, Y. J. Biol. Chem. 261, 1355-1358, 1986). We have investigated membrane localization of bovine platelet factor XIII using immunological techniques. Immunofluorescent visualization revealed that the factor XIII was expressed on the surface of non-permeabilized bovine platelets, where we detected neither lactate dehydrogenase, a cytoplasmic enzyme marker, nor B subunit of factor XIII, which is present in plasma. Cell surface iodination and immunoprecipitation also confirmed that it existed on the surface of platelets.     

Inhibition of murine chronic graft-versus-host disease by the chloroform extract of Tripterygium wilfordii Hook f

The effects of chloroform extract of Tripterygium Wilfordii Hook f (TWH extract) on chronic graft-versus-host disease (GVHD) were examined in a murine experimental model. Chronic GVHD was induced by intravenous transfer of parental DBA/2 spleen cells into unirradiated (C57BL/6 × DBA/2)F1 recipient mice. The effects of TWH extract on GVHD were assessed by measuring both the degree of splenomegaly and the total serum IgE levels 3 weeks after the cell transfer. Subcutaneous administration of TWH extract once a day for 3 weeks suppressed chronic GVHD in a dose-dependent manner. Significant suppression of splenomegaly was first noted in mice treated with 7.5 μg/kg of the agent. The maximum inhibition was observed when mice were treated with more than 10.0 μg/kg (but not 5.0 μg/kg) caused complete suppression of serum IgE hyperproduction. The ability of donor T cells purified from recipient spleen cells to produce interleukin 4 in response to stimulation with anti-CD3 monoclonal antibody was significantly abrogated when recipient mice were treated with 10.0 μg/kg of the agent. These results strongly suggest that TWH extract will be an addition to the cohort of immunosuppressive therapies used in solid organ and bone marrow transplantation.     

Prognostic significance of adoptive immunotherapy with tumor-associated lymphocytes in patients with advanced gastric cancer: a randomized trial.

PURPOSE: We performed adoptive immunotherapy (AIT)with tumor-associated lymphocytes (TALs) in combination with chemotherapy in patients with advanced-stage gastric cancer in a randomized controlled study and investigated whether or not an improved survival effect is observed with AIT. EXPERIMENTAL DESIGN: Forty-four consecutive patients with stage IV gastric cancer [staged according to the International Union against Cancer classification] were prospectively assigned to the control group (chemotherapy alone) or the AIT group (AIT plus chemotherapy). Patients in the AIT group received an adoptive transfer of cultured TALs in combination with low-dose cisplatinum/5-fluorouracil chemotherapy, whereas patients in the control group received chemotherapy alone. RESULTS: The 50% survival rates were 11.5 and 8.3 months in the AIT and control groups, respectively. The overall survival of patients in the AIT group was significantly better than that of patients in the control group, as analyzed by the log-rank test (P < 0.05). Multivariate analysis with Cox's proportional hazards model revealed that AIT provided an independent prognostic factor, indicating that AIT influenced patient survival in a positive manner. CONCLUSIONS: AIT with TALs in combination with chemotherapy was effective in prolonging survival in patients with stage IV gastric cancer.