DX‐8951 is a novel water‐soluble derivative of camptothecin. We evaluated the effects of DX‐8951 on the growth of several pancreatic tumor cell lines in vitro and in vivo. In vitro cytotoxic activity of DX‐8951 against SUIT‐2 and KP‐1N cells, as indicated by IC50 value, was several times more potent than that of SN‐38, an active metabolite of CPT‐11, and dozens of times more potent than that of SK&F104864 (topotecan). DX‐8951 also showed the greatest cytotoxicity against CPT‐11‐resis‐tant variants, SUIT‐2/CPT‐11 and KP‐1N/CPT‐11 cells, and the cross‐resistance of these cells to DX‐8951 was lower than that to SN‐38 and SK&F104864. Topoisomerase 1 inhibitory activity of DX‐8951 was about three‐fold stronger than that of SN‐38, as measured in crude nuclear extract obtained from SUIT‐2 cells. DX‐8951 induced DNA fragmentation, a specific feature of apoptosis, in SUIT‐2 cells more effectively than SN‐38. DX‐8951 exhibited potent antitumor effects against SUIT‐2 in a solid tumor model and in a liver metastasis model, in which tumor cells were xenografted sub‐cutaneously and intrasplenically, respectively, into nude mice. The in vivo effects were closely similar to or somewhat superior to those of CPT‐11, DX‐8951 also showed significant antitumor effects against SUIT‐2/CPT‐11 solid tumors, against which CPT‐11 had no effect. These results suggest that, on the basis of its strong antitumor activity and effectiveness against CPT‐11‐resistant tumors, DX‐8951 may be a useful therapeutic agent in the treatment of human cancer. The potent cytotoxicity of DX‐8951 may result from strong inhibition of topoisomerase I, which may then trigger apoptotic cell death.
The number of patients with diabetes continues to increase in Japan, which means that education in disease management is important. However, there have been few investigations into the importance of hospital pharmacists performing outpatient education for diabetes mellitus in Japan. In the diabetes outpatient department of Kitakyushu City Moji Hospital, a pharmacist commenced patient education using check sheets before patients saw the physicians from 2012. We divided the patients into groups with an increase or decrease of hemoglobin A1c (HbA1c) level after 6 months from the start of patient education. To assess the factors related to a decrease of HbA1c level, we compared background factors, and laboratory values between these two groups. In the patients whose HbA1c level decreased, the level was high at the start of patient education and they had less knowledge about their medications. To evaluate the impact of this patient education, we compared HbA1c values before patient education and after 6 months to determine the eŠect of providing education in the diabetes outpatient department. In the HbA1c8% group, the HbA1c level decreased signiˆcantly during 6 months of patient education. These results suggest that patient education by hospital pharmacists can be eŠective if HbA1c level is high at the start of education. This is theˆrst report about the usefulness of patient education by a hospital pharmacist for improvement of HbA1c level in diabetic outpatients in Japan.
Recombinant mouse/human chimeric monoclonal antibody A10 (ch‐A10) and its Fab fragment (ch‐Fab) react with carcinoembryonic antigen on various gastrointestinal carcinomas. We performed biodistribution studies with 125I‐labeled ch‐Al0 and ch‐Fab in an antigen‐positive human pancreatic carcinoma (BxPC‐3) xenograft model. We also evaluated the anti‐tumor effect of 131I‐labeled ch‐Al0 and studied the detection of BxPC‐3 xenografts with 123I‐labeIed ch‐Fab in whole body scintigraphy. In comparative biodistribution studies, the tumor uptake of 125I‐labeled ch‐Al0 was significantly greater than that of 125I‐labeIed ch‐Fab 24 h post‐injection. However, the tumor‐to‐blood ratio was 46.8 for ch‐Fab at 24 h post‐injection, while it was only 1.4 for ch‐Al0. Microautoradiography studies showed that ch‐Fab penetrated more uniformly into the tumor nodules than did ch‐Al0. In mice given a therapeutic dose of 131I‐labeled ch‐AlO, a significant inhibition of tumor growth was seen, while control I31l‐labeled human IgG did not affect tumor growth. Leukocyte toxicity was observed within 3 weeks after injection of 131I‐labeled ch‐Al0, but leukocyte counts recovered to normal levels at 8 weeks post‐injection. In whole‐body scintigraphy, clear and rapid tumor imaging was obtained with 200 (Ci of 123I‐labeled ch‐Fab 24 h post‐injection. These results suggest that radioiodine‐labeled chimeric A10 antibodies could potentially be useful candidates for radioimmunotherapy and radio‐immunodetection of pancreatic carcinomas.
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