Analytical case study of evaluation of curriculum at a medical school.

PURPOSE: This study aims at to make intermediate-term evaluations of a curriculum by investigating its development, operation and outcomes 2 years after its revision. METHODS: A survey using 5-point-Lickert scale questionnaires was given to the group of directors who developed the curriculum, instructors who only used it in their classes, and a student group from the first and second grades. Focus group interviews were performed in the professor groups. RESULTS: Curricular reform was evaluated as being systematic, democratic, and positive in general. Both groups answered questions positively about the relevance of the integrated curriculum and introduction of clinical medicine (ICM), graded as 3.4 (professor) and 3.5 (student). As for problem-based learning (PBL) and the patient-doctor-society (PDS), the professor group responded more positively than students. The 'web-based learning center' was recognized positively by many more students (4.01) than professors (2.75). With regard to the education outcome, professors gave 3.3 points and students 3.5 to an item that asked 'whether students attained the learning goal or not?' Professors, through interviews, showed their satisfaction with the attempt to reform the curriculum, but they pointed out that long-term evaluations should be performed. CONCLUSION: The interim evaluation of the revised curriculum, from its planning to its effects, affirmed by several suggestions to be successful in the long run through 1) enhancement of systematic participation and communication, 2) further integration, 3) steady evaluation, 4) greater effort on professional development, and 5) active interaction between professors and students.

Enhancement of tumor radioresponse by wortmannin in C3H/HeJ hepatocarcinoma.

The objective of this study was to explore whether a specific inhibitor of PI3K, wortmannin, could potentiate the antitumor effect of radiation in vivo, particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both. Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days. Tumor response to treatment was determined by a tumor growth delay assay. Possible mechanisms of action were explored by examining the level of apoptosis and regulating molecules. The expression of regulating molecules was analyzed by Western blot for p53 and p21(WAF1/CIP1), and immunohistochemical staining for p21(WAF1/CIP1), CD31 and VEGF. In the tumor growth delay assay, wortmannin increased the effect of tumor radioresponse with an enhancement factor (EF) of 2.00. The level of apoptosis achieved by the combined treatments was shown to be no more than an additive effect; peak apoptotic index was 11% in radiation alone, 13% in wortmannin alone, and 19% in the combination group. Markedly increased areas of necrosis at 24 h in the combination group were noted. Western blotting showed upregulation of p21(WAF1/CIP1) in the combination treatment group, which correlated with low levels of VEGF. Microvascular density was evidently also reduced, based on low expression of CD31. In murine hepatocarcinoma, the antitumor effect of radiation was potentiated by wortmannin. The mechanism seems to involve not only the increase of induced apoptosis but also enhanced vascular injury. Wortmannin, in combination with radiation therapy, may have potential benefits in cancer treatment.

Alteration of cancer pain-related signals by radiation: proteomic analysis in an animal model with cancer bone invasion.

PURPOSE: Although radiotherapy is highly effective in relieving bone pain due to cancer invasion, its mechanism remains unclear. The aim of this study was to explore this mechanism in an animal model system. METHODS AND MATERIALS: A hind paw model of cancer pain was developed by transplanting a murine hepatocarcinoma, HCa-1, into the periosteal membrane of the foot dorsum of C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed from sequential tumor sampling. For three experimental groups, a control (N), tumor without radiation (T), and tumor with radiation (TR), the development and level of pain were objectively examined in mice with a growing tumor by assessing pain-associated behavior. The differential expression of pain-related signals in the spinal cord was analyzed by proteomic analysis using high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry, and those of proteins by Western blotting. The pain-mediating neurotransmitters in the spinal cord were also examined by immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P. RESULTS: In the histopathologic examinations, bone invasion from HCa-1 was seen from Day 7 and was evident at Day 14 after transplantation, and measurable pain-associated behaviors were developed from Day 7. After 25 Gy of radiation to the tumors, the objective level of pain in the TR group decreased, with higher thresholds to mechanical and thermal stimulation than in the T group. From the 2-DE of spinal cord, 107 spots were identified; 12 proteins were changed more than fivefold because of tumor formation but then reversed after radiation in the tumor-bearing mice. The proteins involved included secretagogin, syntenin, P2X purinoreceptor 6 (P2X6), and Ca(2+)/Calmodulin-dependent protein kinase 1 (CaM kinase 1), the functions of which have been known to be involved in the Ca(2+)-signaling cascade, ATP-mediated fast synaptic transmission, or control of vesicular trafficking. Validations using Western blotting were successful for the CaM kinase and P2X6. In immunohistochemical staining of the spinal cord, a significant decrease after irradiation was shown in the expression of CGRP, but not in substance P. CONCLUSIONS: We developed a novel model for bone pain due to cancer invasion, which was confirmed by histopathologic examination and measurable pain-associated behaviors. Radiotherapy decreased the objective level of pain. The underlying mechanism seems to be related to the Ca(2+)-signaling cascade or control of vesicular trafficking.