Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.

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Dolastatin 10, a pentapeptide isolated from the marine mollusk Dolabella auricularia, has antitumor activity. TZT‐1027, a dolastatin 10 derivative, is a newly synthesized antitumor compound. We evaluated its antitumor activity against a variety of transplantable tumors in mice. Intermittent injections of TZT‐1027 were more effective than single or repeated injections in rake with P388 leukemia and B16 melanoma. Consequently, TZT‐1027 shows schedule dependency. TZT‐1027 was effective against P388 leukemia not only when administered i.p., but also when given i.v. However, although TZT‐1027 given i.v. was active against murine solid tumors, TZT‐1027 administered i.p. was ineffective against all the tumors tested with the exception of colon 26 adenocarcinoma. The i.v. injection of TZT‐1027 at a dose of 2.0 mg/Ag remarkably inhibited the growth of three murine solid tumors; colon 26 adenocarcinoma, B16 melanoma and M5076 sarcoma, with T/C values of less than 6%. The antitumor activities of TZT‐1027 against these tumors were superior or comparable to those of the reference agents; dolastatin 10, cisplatin, vincristine, 5‐fluorouracil (5‐FU) and E7010. In experiments with drug‐resistant P388 leukemia, TZT‐1027 showed good activity against cisplatin‐resistant P388 and moderate activity against vincristine‐ and 5‐fluorouracil‐resistant P388, but no activity against adriamycin‐resistant P388. TZT‐1027 was also effective against human xenografts, that is, tumor regression was observed in mice bearing MX‐1 breast and LX‐1 lμng carcinomas. TZT‐1027 at 10 μM almost completely inhibited the assembly of porcine brain microtubules. Therefore, its mechanism of antitumor action seems to he, at least in part, ascrihable to the inhibition of microtubule assembly. Because of its good preclinical activity, TZT‐1027 has been entered into phase I clinical trials.

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Introduction:The declining number of family physicians providing pregnancy care is of concern because they are an important source of pregnancy care in underserved communities. Innovative approaches might reinforce family physician participation in pregnancy care for the underserved. Since group prenatal visits have been shown to improve patient education, support, and satisfaction, we implemented and evaluated a group prenatal visit program for Japanese women in Michigan, an underserved population because of their limited proficiency with English.Methods: We conducted a convergent quantitative and qualitative mixed methods evaluation involving repeated survey administration (program evaluations, 4-item Patient Health Questionnaire, pregnancy distress questionnaire) to participants during 5 group visits and in-depth postpartum interviews in the University of Michigan Japanese Family Health Program setting. We conducted independent quantitative and qualitative analytics and then thematically integrated these data.Results: Cultural adaptations to the Centering Pregnancy format involved changes in total visits, educational content, and participation format. Based on 5 groups attending 5 sessions each, 42 women evaluated the program through 158 surveys after the sessions. Participants evaluated multiple parameters positively: being with other pregnant women (98%), improving their understanding about prenatal care (96%), preparation for labor and delivery (96%), organization of visits (94%), and preparation for newborn care (85%). In final evaluations, 96% to 100% of participants rated 7 educational topics as "covered" or "covered well." Qualitative interviews with 20 women revealed positive views of social support from prenatal group visits and group facilitation but mixed enthusiasm for clinical assessments in the prenatal group visit setting and partner and children attendance at the sessions.Conclusions: This research demonstrates the feasibility and cultural acceptability of prenatal group visits for Japanese women. Prenatal group visits provided education and social support for Japanese women during the perinatal and postpartum periods that were not otherwise accessible in Japanese. This study confirms the feasibility of family physicians providing prenatal group visits and extends the literature of the applicability of prenatal group visits for patients with limited English skills. Family physicians train to provide the full breadth of care for common problems across the life span and are particularly recognized as apropos in isolated rural communities and underserved populations. As with family physicians providing care for a geographically isolated population, a bilingual family physician can also be particularly effective for linguistically and culturally isolated groups regardless of rural or urban setting.Family physicians have long been considered an important source of maternity care, particularly in rural and underserved settings. [5][6][7] The number of family physicians providing maternity care is un...

Three-dimensional structures of vacuum-deposited Cu species formed on TiO 2 (110) surfaces premodified with three mercaptobenzoic acid (MBA) isomers were studied using polarization-dependent total reflection fluorescence X-ray absorption fine structure (PTRF-XAFS) . We explored the possibility of fine tuning and orientation control of the surface Cu structures, including their coordination and

In Item Response Theory (IRT), item characteristic curves (ICCs) are illustrated through logistic models or normal ogive models, and the probability that examinees give the correct answer is usually a monotonically increasing function of their ability parameters. However, since only limited patterns of shapes can be obtained from logistic models or normal ogive models, there is a possibility that the model applied does not fit the data. As a result, the existing method can be rejected because it cannot deal with various item response patterns.To overcome these problems, we propose a new semiparametric IRT model using a Dirichlet process mixture logistic distribution. Our method does not rely on assumptions but only requires that the ICCs be a monotonically nondecreasing function; that is, our method can deal with more types of item response patterns than the existing methods, such as the one-parameter normal ogive models or the two-or threeparameter logistic models.We conducted two simulation studies whose results indicate that the proposed method can express more patterns of shapes for ICCs and can estimate the ability parameters more accurately than the existing parametric and nonparametric methods. The proposed method has also been applied to Facial Expression Recognition data with noteworthy results.